Phenotypes associated with this allele

• Allele Symbol: Pten^tm1Hwu
• Allele Name: targeted mutation 1, Hong Wu
• Allele ID: MGI:2156086
• Summary: 159 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Pten^tm1Hwu/Pten^+	involves: 129S4/SvJae * BALB/c	MGI:3707147
cn2	Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S4/SvJae	MGI:4848150
cn3	Kdr^tm1Jrt/Kdr^+ Pten^tm1Hwu/Pten^tm1Hwu Twist2^tm1.1(cre)Dor/Twist2^+	B6.129-Twist2^tm1.1(cre)Dor Kdr^tm1Jrt Pten^tm1Hwu	MGI:5503216
cn4	Pten^tm1Hwu/Pten^tm1Hwu Twist2^tm1.1(cre)Dor/Twist2^+	B6.129-Twist2^tm1.1(cre)Dor Pten^tm1Hwu	MGI:5503192
cn5	Pten^tm1Hwu/Pten^tm1Hwu Tg(Gdf9-icre)5092Coo/0	B6.Cg-Pten^tm1Hwu Tg(Gdf9-icre)5092Coo	MGI:4839213
cn6	Pten^tm1Hwu/Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand/0	B6.Cg-Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand	MGI:5517706
cn7	Pten^tm1Hwu/Pten^+ Tg(Nkx2-1-cre)2Sand/0	B6.Cg-Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand	MGI:5517709
cn8	Pten^tm1Hwu/Pten^tm1Hwu Tg(Tyr-cre)1Lru/0	B6.Cg-Pten^tm1Hwu Tg(Tyr-cre)1Lru	MGI:4882033
cn9	Pten^tm1Hwu/Pten^tm1Hwu Tg(Zp3-cre)93Knw/0	B6.Cg-Pten^tm1Hwu Tg(Zp3-cre)93Knw	MGI:4882031
cn10	Nf1^tm1Fcr/Nf1^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Mx1-cre)1Cgn/0	B6.Cg-Tg(Mx1-cre)1Cgn Nf1^tm1Fcr Pten^tm1Hwu	MGI:5787929
cn11	Pten^tm1Hwu/Pten^tm1Hwu Tg(Mx1-cre)1Cgn/0	B6.Cg-Tg(Mx1-cre)1Cgn Pten^tm1Hwu	MGI:5787932
cn12	Cnp^tm1(cre)Kan/Cnp^+ Pten^tm1Hwu/Pten^tm1Hwu	B6N.129-Cnp^tm1(cre)Kan Pten^tm1Hwu	MGI:5902387
cn13	Pten^tm1Hwu/Pten^tm1Hwu Cop1^tm2.1Vmd/Cop1^tm2.1Vmd Tg(Pbsn-cre)4Prb/0	B6N.CgCop1^tm2.1Vmd Pten^tm1Hwu Tg(Pbsn-cre)4Prb	MGI:5013604
cn14	Pten^tm1Hwu/Pten^tm1Hwu Tg(Mx1-cre)1Cgn/0	BKS.Cg-Ptprc^b Thy1^a Tg(Mx1-cre)1Cgn Pten^tm1Hwu	MGI:4839500
cn15	Pik3ca^tm1Jjz/Pik3ca^tm1Jjz Pik3cb^tm1Jjz/Pik3cb^tm1Jjz Pten^tm1Hwu/Pten^tm1Hwu Tg(KRT14-cre)#Smr/0	FVB.Cg-Pik3ca^tm1Jjz Pik3cb^tm1Jjz Pten^tm1Hwu Tg(KRT14-cre)#Smr	MGI:5506907
cn16	Pik3ca^tm1Jjz/Pik3ca^tm1Jjz Pten^tm1Hwu/Pten^tm1Hwu Tg(KRT14-cre)#Smr/0	FVB.Cg-Pik3ca^tm1Jjz Pten^tm1Hwu Tg(KRT14-cre)#Smr	MGI:5506905
cn17	Pik3cb^tm1Jjz/Pik3cb^tm1Jjz Pten^tm1Hwu/Pten^tm1Hwu Tg(KRT14-cre)#Smr/0	FVB.Cg-Pik3cb^tm1Jjz Pten^tm1Hwu Tg(KRT14-cre)#Smr	MGI:5506906
cn18	Pten^tm1Hwu/Pten^tm1Hwu Tg(KRT14-cre)#Smr/0	FVB.Cg-Pten^tm1Hwu Tg(KRT14-cre)#Smr	MGI:5506904
cn19	Calca^tm1.1(cre/ERT2)Ptch/Calca^+ Trp53^tm1Brn/Trp53^tm1Brn Rb1^tm2Brn/Rb1^tm2Brn Pten^tm1Hwu/Pten^tm1Hwu	involves: 129 * 129P2/OlaHsd * 129S4/SvJae * BALB/c * FVB/N	MGI:5460854
cn20	Gt(ROSA)26Sor^tm1(cre/ERT)Nat/Gt(ROSA)26Sor^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129 * 129S4/SvJae * BALB/c * C57BL/6	MGI:4847601
cn21	Pten^tm1Hwu/Pten^tm1Hwu Tgfbr1^tm1.1Karl/Tgfbr1^tm1.1Karl Tg(KRT14-cre/ERT)20Efu/0	involves: 129 * 129S4/SvJae * C57BL/6 * CD-1 * FVB/N	MGI:5487550
cn22	Hspa5^tm1Alee/Hspa5^tm1.1Alee Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/?	involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2	MGI:4943512
cn23	Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/0	involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2	MGI:3805865
cn24	Hspa5^tm1Alee/Hspa5^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/?	involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2	MGI:4943514
cn25	Hspa5^tm1Alee/Hspa5^tm1Alee Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/?	involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2	MGI:4943513
cn26	Pten^tm1Hwu/Pten^tm1Hwu Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-cre)1Jaw/0	involves: 129 * 129S4/SvJae * C57BL/6 * FVB/N	MGI:4882116
cn27	Pgr^tm2(cre)Lyd/Pgr^+ Pten^tm1Hwu/Pten^tm1Hwu Trp53^tm1Brn/Trp53^tm1Brn	involves: 129 * C57BL/6	MGI:3813634
cn28	Igs2^tm1(CAG-Met)Zsu/Igs2^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/0	involves: 129 * C57BL/6 * DBA/2 * FVB/N	MGI:6507866
cn29	Cd19^tm1(cre)Cgn/Cd19^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:4829791
cn30	Pten^tm1Hwu/Pten^tm1Hwu Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:4836609
cn31	Cd19^tm1(cre)Cgn/Cd19^+ Inpp5d^tm1Rav/Inpp5d^tm1Rav Pten^tm1Hwu/Pten^tm1Hwu	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:5013951
cn32	Cd19^tm1(cre)Cgn/Cd19^tm1(cre)Cgn Pten^tm1Hwu/Pten^tm1Hwu	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:4829792
cn33	Braf^tm1Mmcm/Braf^tm1Mmcm Nkx3-1^tm4(cre/ERT2)Mms/Nkx3-1^+ Pten^tm1Hwu/Pten^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:5543907
cn34	Dicer1^tm1Tara/Dicer1^tm1Tara Pten^tm1Hwu/Pten^tm1Hwu Amhr2^tm3(cre)Bhr/Amhr2^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd	MGI:5704363
cn35	Dicer1^tm1Tara/Dicer1^tm1Tara Pten^tm1Hwu/Pten^tm1Hwu Trp53^tm2Tyj/Trp53^+ Amhr2^tm3(cre)Bhr/Amhr2^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd	MGI:5704370
cn36	Pten^tm1Hwu/Pten^tm1Hwu Trp53^tm2Tyj/Trp53^+ Amhr2^tm3(cre)Bhr/Amhr2^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd	MGI:5704372
cn37	Cd19^tm1(cre)Cgn/Cd19^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:5007685
cn38	Pten^tm1Hwu/Pten^tm1Hwu Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho Tg(Mx1-cre)1Cgn/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA	MGI:4944270
cn39	Akt2^tm1.1Mbb/Akt2^tm1.1Mbb Pten^tm1Hwu/Pten^tm1Hwu Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA	MGI:4838529
cn40	Pten^tm1Hwu/Pten^tm1Hwu Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB	MGI:3844324
cn41	Nf1^tm1Par/Nf1^+ Pten^tm1Hwu/Pten^+ Trp53^tm1Tyj/Trp53^+ Tg(GFAP-cre)25Mes/0	involves: 129S1/Sv * 129S2/SvPas * 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4840094
cn42	Pten^tm1Hwu/Pten^tm1Hwu Tg(CAG-Bgeo/ALPP)1Lbe/0 Tg(Cela1-cre/ERT)1Dam/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4836240
cn43	Pten^tm1Hwu/Pten^tm1Hwu Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4836647
cn44	Errfi1^tm1Jwj/Errfi1^tm1Jwj Pgr^tm2(cre)Lyd/Pgr^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4944273
cn45	Pten^tm1Hwu/Pten^tm1Hwu Scgb1a1^tm1.1(cre)Fjd/Scgb1a1^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4839214
cn46	Pgr^tm2(cre)Lyd/Pgr^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4944272
cn47	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^tm1Hwu Scgb1a1^tm1.1(cre)Fjd/Scgb1a1^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4839216
cn48	Ctnnb1^tm2Kem/Ctnnb1^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Cdh5-cre)7Mlia/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6 * FVB/N	MGI:4839562
cn49	Ctnnb1^tm2Kem/Ctnnb1^tm2Kem Pten^tm1Hwu/Pten^tm1Hwu Tg(Cdh5-cre)7Mlia/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6 * FVB/N	MGI:4839561
cn50	Nf1^tm1Par/Nf1^+ Pten^tm1Hwu/Pten^+ Tg(Gfap-cre)77.6Mvs/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6NHsd	MGI:4849443
cn51	Pgr^tm2(cre)Lyd/Pgr^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6	MGI:3813633
cn52	Gt(ROSA)26Sor^tm1(CAG-Errfi1)Jwj/? Pgr^tm2(cre)Lyd/Pgr^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6	MGI:5780554
cn53	Ar^tm1Verh/Y Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2	MGI:5009703
cn54	Nf1^tm1Par/Nf1^+ Pten^tm1Hwu/Pten^+ Trp53^tm1Elee/Trp53^+ Tg(GFAP-cre)25Mes/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4840096
cn55	Erbb2^tm8(Erbb2)Mul/Erbb2^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(MMTV-cre)7Mul/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4839510
cn56	Erbb2^tm8(Erbb2)Mul/Erbb2^+ Pten^tm1Hwu/Pten^+ Tg(MMTV-cre)7Mul/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4839508
cn57	Bcl2l11^tm1.1Ast/Bcl2l11^+ Pten^tm1Hwu/Pten^+ Tg(CD2-icre)4Kio/0	involves: 129S1/Sv * 129S4/SvJae * C57BL/10 * CBA/Ca	MGI:3783573
cn58	Pten^tm1Hwu/Pten^tm1Hwu Ptpn11^tm1Gsf/Ptpn11^tm1Gsf Tg(Six3-cre)69Frty/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:6384016
cn59	Pten^tm1Hwu/Pten^tm1Hwu Tg(Pdx1-cre)89.1Dam/0 Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6 * CBA	MGI:4836239
cn60	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Pten^tm1Hwu/Pten^tm1Hwu Tg(Fabp1-cre)1Jig/0	involves: 129S2/SvPas * 129S4/SvJae * FVB/N	MGI:4844100
cn61	Pten^tm1Hwu/Pten^tm1Hwu Tg(Fabp4-cre)1Abel/0	involves: 129S4/SvJae	MGI:4830361
cn62	Pten^tm1Hwu/Pten^tm1Hwu Tg(MMTV-cre)#Tfln/0	involves: 129S4/SvJae	MGI:5688693
cn63	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S4/SvJae	MGI:5014516
cn64	Fas^tm1Ach/Fas^tm1Ach Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S4/SvJae	MGI:5014515
cn65	Pten^tm1Hwu/Pten^tm1Hwu Tg(Pgc-cre,-secNluc)#Hcz/0	involves: 129S4/SvJae	MGI:7543156
cn66	Pten^tm1Hwu/Pten^tm1Hwu Tg(Cr2-cre)3Cgn/0	involves: 129S4/SvJae	MGI:4430559
cn67	Pten^tm1Hwu/Pten^tm1Hwu Tg(CYP19A1-cre)1Jri/0	involves: 129S4/SvJae	MGI:4847591
cn68	Gt(ROSA)26Sor^tm1(Notch1)Dam/Gt(ROSA)26Sor^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Adipoq-cre)1Evdr/0	involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6J * FVB/NJ	MGI:5816455
cn69	Foxo1^tm1Rdp/Foxo1^tm1.1Rdp Foxo3^tm1Rdp/Foxo3^tm1.1Rdp Pten^tm1Hwu/Pten^tm1Hwu Tg(CYP19A1-cre)1Jri/0	involves: 129S4/SvJae * 129S6/SvEvTac	MGI:5784501
cn70	Pten^tm1Hwu/Pten^tm1Hwu Rictor^tm1.1Mgn/Rictor^tm1.1Mgn	involves: 129S4/SvJae * 129S6/SvEvTac	MGI:4848147
cn71	Pten^tm1Hwu/Pten^tm1Hwu Rictor^tm1.1Mgn/Rictor^tm1.1Mgn Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * 129S6/SvEvTac * BALB/c * C57BL/6 * DBA	MGI:5008147
cn72	Nkx3-1^tm4(cre/ERT2)Mms/Nkx3-1^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:4365721
cn73	Eif2ak3^tm1.2Drc/Eif2ak3^tm1.2Drc Pten^tm1Hwu/Pten^tm1Hwu Tg(CAG-MYC,-GFP*)#Rugg/0 Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA/2	MGI:6198768
cn74	Pten^tm1Hwu/Pten^tm1Hwu Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Alb1-cre)1Dlr/0	involves: 129S4/SvJae * 129S6/SvEvTac * FVB/N	MGI:4839217
cn75	Pten^tm1Hwu/Pten^tm1Hwu Amhr2^tm3(cre)Bhr/Amhr2^+	involves: 129S4/SvJae * 129S7/SvEvBrd	MGI:4942351
cn76	Amhr2^tm3(cre)Bhr/Amhr2^+ Ctnnb1^tm1Mmt/Ctnnb1^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S4/SvJae * 129S7/SvEvBrd * 129X1/SvJ	MGI:4941746
cn77	Amhr2^tm3(cre)Bhr/Amhr2^+ Ctnnb1^tm1Mmt/Ctnnb1^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S4/SvJae * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6	MGI:5432232
cn78	Amhr2^tm3(cre)Bhr/Amhr2^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6	MGI:5013567
cn79	Ctnnb1^tm1Mmt/Ctnnb1^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(CYP19A1-cre)1Jri/0	involves: 129S4/SvJae * 129X1/SvJ * C57BL/6	MGI:5432226
cn80	Ctnnb1^tm1Mmt/Ctnnb1^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Upk2-cre)6Xrw/0	involves: 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4943270
cn81	Ctnnb1^tm1Mmt/Ctnnb1^tm1Mmt Pten^tm1Hwu/Pten^tm1Hwu Tg(Upk2-cre)6Xrw/0	involves: 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4943268
cn82	Pten^tm1Hwu/Pten^+ Tg(Nkx2-1-cre)2Sand/0	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:5517675
cn83	Pten^tm1Hwu/Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand/0	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:5014514
cn84	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^+ Tg(Pdx1-cre)89.1Dam/0	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:5013916
cn85	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Pdx1-cre)89.1Dam/0	involves: 129S4/SvJae * BALB/c * C57BL/6 * CBA	MGI:5013917
cn86	Pten^tm1Hwu/Pten^tm1Hwu Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA	MGI:5008144
cn87	Pten^tm1Hwu/Pten^tm1Hwu Tg(CAG-fat-1)1Jxk/0 Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2	MGI:4847617
cn88	Pten^tm1Hwu/Pten^+ Tg(ARR2/Pbsn-FGF8)3Prb/0 Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2	MGI:4843916
cn89	Pten^tm1Hwu/Pten^+ Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2	MGI:4420975
cn90	Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2	MGI:4420974
cn91	Pten^tm1Hwu/Pten^tm1Hwu Tg(Cdh5-cre)7Mlia/0	involves: 129S4/SvJae * BALB/c * C57BL/6 * FVB/N	MGI:4839560
cn92	Pten^tm1Hwu/Pten^tm1Hwu Tg(Camk2a-cre)T50Stl/0 Tg(Thy1-EGFP)MJrs/0	involves: 129S4/SvJae * BALB/c * C57BL/6J * CBA	MGI:4942301
cn93	Pten^tm1Hwu/Pten^tm1Hwu Vhl^tm1Jae/Vhl^tm1Jae Tg(Cdh16-cre)91Igr/0	involves: 129S4/SvJae * BALB/c * C57BL/6J * ICR	MGI:4943534
cn94	Pten^tm1Hwu/Pten^tm1Hwu Tg(Cdh16-cre)91Igr/0	involves: 129S4/SvJae * BALB/c * C57BL/6J * ICR	MGI:4943546
cn95	Pten^tm1Hwu/Pten^tm1Hwu Tg(Vil1-cre)997Gum/0	involves: 129S4/SvJae * BALB/c * C57BL/6J * SJL	MGI:4941760
cn96	Apc^Min/Apc^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Vil1-cre)997Gum/0	involves: 129S4/SvJae * BALB/c * C57BL/6J * SJL	MGI:4941759
cn97	Pten^tm1Hwu/Pten^tm1Hwu Tg(Gfap-cre)77.6Mvs/0	involves: 129S4/SvJae * BALB/c * C57BL/6NHsd	MGI:3838843
cn98	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^+ Tg(Gfap-cre)77.6Mvs/0	involves: 129S4/SvJae * BALB/c * C57BL/6NHsd	MGI:4849441
cn99	Pten^tm1Hwu/Pten^tm1Hwu Tg(Scgb1a1-cre)1Tauc/0	involves: 129S4/SvJae * C57BL/6	MGI:4943565
cn100	Pten^tm1Hwu/Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand/0	involves: 129S4/SvJae * C57BL/6	MGI:4836606
cn101	Pten^tm1Hwu/Pten^tm1Hwu Slc6a3^tm1.1(cre)Bkmn/Slc6a3^+	involves: 129S4/SvJae * C57BL/6	MGI:4849440
cn102	Pten^tm1Hwu/Pten^tm1Hwu Tg(Gdf9-icre)5092Coo/0	involves: 129S4/SvJae * C57BL/6	MGI:4882032
cn103	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Scgb1a1-cre)1Tauc/0	involves: 129S4/SvJae * C57BL/6	MGI:4943568
cn104	Gt(ROSA)26Sor^tm9(cre/ESR1)Arte/Gt(ROSA)26Sor^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S4/SvJae * C57BL/6	MGI:5008585
cn105	Gt(ROSA)26Sor^tm1(H1/tetO-RNAi:Pdpk1)Mrl/Gt(ROSA)26Sor^tm9(cre/ESR1)Arte Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S4/SvJae * C57BL/6	MGI:5008587
cn106	Pten^tm1Hwu/Pten^tm1Hwu Tg(CD2-icre)4Kio/0	involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca	MGI:5688871
cn107	Pkn3^tm1.1Mrl/Pkn3^tm1.1Mrl Pten^tm1Hwu/Pten^tm1Hwu Tg(CD2-icre)4Kio/0	involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca	MGI:5688869
cn108	Pten^tm1Hwu/Pten^tm1Hwu Tg(Mx1-cre)1Cgn/0	involves: 129S4/SvJae * C57BL/6 * C57BL/6J * CBA	MGI:5007630
cn109	Pten^tm1Hwu/Pten^tm1Hwu Tg(CAG-MYC,-GFP*)#Rugg/0 Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * C57BL/6 * C57BL/6J * DBA/2	MGI:6198766
cn110	Mirc14^tm1.1Flv/Mirc14^tm1.1Flv Pten^tm1Hwu/Pten^tm1Hwu Tg(Cd4-cre)1Cwi/0	involves: 129S4/SvJae * C57BL/6 * C57BL/6N * DBA/2 * SJL	MGI:5529025
cn111	Lepr^db/Lepr^db Pten^tm1Hwu/Pten^tm1Hwu Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C57BL/6 * C57BLKS/J * DBA	MGI:5013485
cn112	Pten^tm1Hwu/Pten^tm1Hwu Tg(Mx1-cre)1Cgn/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:4836620
cn113	Pten^tm1Hwu/Pten^tm1Hwu Tg(Pdx1-cre/Esr1*)35.10Dam/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:4836238
cn114	Apc^tm1Tno/Apc^tm1Tno Pten^tm1Hwu/Pten^tm1Hwu Tg(Cyp1a1-cre/ERT)1Dwi/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:4943267
cn115	Pten^tm1Hwu/Pten^tm1Hwu Tg(Pdx1-cre)89.1Dam/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:4836237
cn116	Pkn3^tm1.1Mrl/Pkn3^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Mx1-cre)1Cgn/0	involves: 129S4/SvJae * C57BL/6 * CBA/J	MGI:5688868
cn117	Pkn3^tm1.1Mrl/Pkn3^tm1.1Mrl Pten^tm1Hwu/Pten^tm1Hwu Tg(Mx1-cre)1Cgn/0	involves: 129S4/SvJae * C57BL/6 * CBA/J	MGI:5688867
cn118	Pten^tm1Hwu/Pten^tm1Hwu Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * DBA	MGI:4829790
cn119	Pten^tm1Hwu/Pten^tm1Hwu Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C57BL/6 * DBA	MGI:4839070
cn120	Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:4358249
cn121	Gt(ROSA)26Sor^tm2(H1/tetO-RNAi:Pdpk1)Mrl/Gt(ROSA)26Sor^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5008589
cn122	Gt(ROSA)26Sor^tm1(H1/tetO-RNAi:Pdpk1)Mrl/Gt(ROSA)26Sor^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5008586
cn123	Pten^tm1Hwu/Pten^+ Tmprss2^tm2.1(ETV1)Sho/Tmprss2^tm2.1(ETV1)Sho Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5578649
cn124	Erg^tm1.1Sho/Erg^tm1.1Sho Pten^tm1Hwu/Pten^tm1Hwu Tmprss2^tm3Sho/Tmprss2^tm3Sho Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5578652
cn125	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5705321
cn126	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^+ Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5705328
cn127	Pten^tm1Hwu/Pten^tm1Hwu Tg(Plp1-cre/ERT2)1Ueli/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:4837112
cn128	Pten^tm1Hwu/Pten^tm1Hwu Ptpn1^tm1Bpk/Ptpn1^tm1Bpk Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:6378626
cn129	Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)20Fwan/?	involves: 129S4/SvJae * C57BL/6 * FVB/NCrl	MGI:5827768
cn130	Gt(ROSA)26Sor^tm1(JAG1)Xin/Gt(ROSA)26Sor^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)20Fwan/?	involves: 129S4/SvJae * C57BL/6 * FVB/NCrl	MGI:5827766
cn131	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S4/SvJae * C57BL/6J	MGI:4836596
cn132	Pten^tm1Hwu/Pten^tm1Hwu Tg(Gdf9-icre)5092Coo/?	involves: 129S4/SvJae * C57BL/6J	MGI:4941739
cn133	Pdpk1^tm1Maka/Pdpk1^tm1Maka Pten^tm1Hwu/Pten^tm1Hwu Tg(Zp3-cre)93Knw/0	involves: 129S4/SvJae * C57BL/6J	MGI:5013920
cn134	Pten^tm1Hwu/Pten^tm1Hwu Tsc1^tm1Djk/Tsc1^tm1Djk Tg(Gdf9-icre)5092Coo/?	involves: 129S4/SvJae * C57BL/6J	MGI:4941741
cn135	Pten^tm1Hwu/Pten^tm1Hwu Tg(Adipoq-cre)1Evdr/0	involves: 129S4/SvJae * C57BL/6J * FVB/NJ	MGI:5816458
cn136	Pten^tm1Hwu/Pten^+ Tg(KRT14-cre)#Smr/0	involves: 129S4/SvJae * C57BL/6J * SJL/J	MGI:3813526
cn137	Pten^tm1Hwu/Pten^tm1Hwu Tg(KRT14-cre)#Smr/0	involves: 129S4/SvJae * C57BL/6J * SJL/J	MGI:3813525
cn138	Pten^tm1Hwu/Pten^tm1Hwu Tg(MMTV-cre)4Mam/0	involves: 129S4/SvJae * FVB	MGI:4829793
cn139	Pten^tm1Hwu/Pten^tm1Hwu Tg(Ckmm-cre)5Khn/?	involves: 129S4/SvJae * FVB	MGI:4944271
cn140	Pten^tm1Hwu/Pten^tm1Hwu A1cf^Tg(Myh6-cre/Esr1*)1Jmk/A1cf^+	involves: 129S4/SvJae * FVB/N	MGI:4882047
cn141	Pten^tm1Hwu/Pten^tm1Hwu Tg(MMTV-cre)7Mul/0	involves: 129S4/SvJae * FVB/N	MGI:4839512
cn142	Pten^tm1Hwu/Pten^tm1Hwu Tg(Alb1-cre)1Dlr/0	involves: 129S4/SvJae * FVB/N	MGI:4839218
cn143	Pten^tm1Hwu/Pten^tm1Hwu Tg(GZMB-cre)1Jcb/0	involves: 129S4/SvJae * FVB/N	MGI:5013915
cn144	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^+ Tg(Upk2-cre)6Xrw/0	involves: 129S4/SvJae * FVB/N	MGI:5141742
cn145	Pten^tm1Hwu/Pten^tm1Hwu Tg(GFAP-cre)25Mes/0	involves: 129S4/SvJae * FVB/N	MGI:4830362
cn146	Pten^tm1Hwu/Pten^tm1Hwu Tg(Nes-cre)1Atp/0	involves: 129S4/SvJae * FVB/N	MGI:4829794
cn147	Pten^tm1Hwu/Pten^tm1Hwu Tg(Ddx4-cre)1Dcas/0	involves: 129S4/SvJae * FVB/N	MGI:4882148
cn148	Pten^tm1Hwu/Pten^tm1Hwu Tg(Ddx4-cre/ERT2)1Dcas/0	involves: 129S4/SvJae * FVB/N	MGI:4882150
cn149	Pten^tm1Hwu/Pten^tm1Hwu Tg(Fabp1-cre)1Jig/0	involves: 129S4/SvJae * FVB/N	MGI:4844083
cn150	Pten^tm1Hwu/Pten^tm1Hwu Tg(TPO-cre)1Shk/0	involves: 129S4/SvJae * FVB/NCr	MGI:5294347
cn151	Pten^tm1Hwu/Pten^tm1Hwu Tg(CAG-EGFP,-PAX8/PPARG)1Rkoe/0 Tg(TPO-cre)1Shk/0	involves: 129S4/SvJae * FVB/NCr * FVB/NJ	MGI:5294346
cn152	Pten^tm1Hwu/Pten^tm1Hwu Vhl^tm1Jae/Vhl^tm1Jae Tg(Cdh16-cre)91Igr/0	involves: 129S4/SvJae * ICR	MGI:4839497
cn153	Pten^tm1Hwu/Pten^tm1Hwu Tg(Cdh16-cre)91Igr/0	involves: 129S4/SvJae * ICR	MGI:4839499
cn154	Gt(ROSA)26Sor^tm2Thl/Gt(ROSA)26Sor^+ Pten^tm1Hwu/Pten^tm1Hwu Tyr^c-Brd/Tyr^c-Brd	involves: 129/Sv * 129S4/SvJae * C57BL/6	MGI:5008633
cn155	Gt(ROSA)26Sor^tm2Thl/Gt(ROSA)26Sor^+ Pten^tm1Hwu/Pten^tm1Hwu Trp53^tm1Thl/Trp53^tm1Thl Tyr^c-Brd/Tyr^c-Brd	involves: 129/Sv * 129S4/SvJae * C57BL/6	MGI:5008634
cn156	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Col1a1^tm1(CAG-EGFR)Char/Col1a1^tm1(CAG-EGFR)Char Pten^tm1Hwu/Pten^tm1Hwu	involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL	MGI:3837855
cn157	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Col1a1^tm2(CAG-EGFR*)Char/Col1a1^tm2(CAG-EGFR*)Char Pten^tm1Hwu/Pten^tm1Hwu	involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL	MGI:3837856
cn158	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Col1a1^tm1(CAG-EGFR)Char/Col1a1^tm2(CAG-EGFR*)Char Pten^tm1Hwu/Pten^tm1Hwu	involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL	MGI:3837857
cx159	Pik3ca^tm1.1Waph/Pik3ca^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S1/Sv * 129S4/SvJae * BALB/c * C57BL/6	MGI:5427585

Genotype
MGI:3707147

ht1

• Allelic Composition: Pten^tm1Hwu/Pten⁺
• Genetic Background: involves: 129S4/SvJae * BALB/c

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

neoplasm

abnormal tumor incidence ( J:110567 )

• Background Sensitivity: spectrum of tumor incidence and onset on the BALB/c background are similar to Pten^tm1.1Hwu on the BALB/c background in the first seven months

Genotype
MGI:4848150

cn2

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S4/SvJae

neoplasm

increased prostate gland adenocarcinoma incidence ( J:144810 )

♂ • prostate adenocarcinoma is seen by 9-10 weeks of age in mutants infected with an adenovirus expressing Cre recombinase

increased prostate intraepithelial neoplasia incidence ( J:144810 )

♂ • mutants infected with an adenovirus expressing Cre recombinase develop PIN by 7 weeks of age

muscle

abnormal muscle fiber morphology ( J:169364 )

• primary myotube cultures treated with adenovirus-cre to delete Pten results in increased myotube size

• primary myotube cultures treated with adenovirus-cre do not exhibit the palmitate-induced decrease in cell size seen in control myotubes

homeostasis/metabolism

abnormal response to injury ( J:165283 )

• mice injected neonatally with a cre-expressing adenovirus into the sensorimotor cortex and undergoing pyramidotomy in adulthood exhibit an increase in trans-midline sprouting of adult corticospinal tract axons compared to controls

• neonatal and postnatal deletion of Pten by injecting cre-expressing adenovirus into the sensorimotor cortex at the neonatal stage or 4 weeks of age, respectively, results in increased corticospinal tract regeneration following T8 complete spinal cord crush injury compared to controls

• the increase in corticospinal tract regeneration is seen when complete spinal cord crush is done at 2 and 5 months of age and the regenerating axons follow ectopic trajectories and extend bilaterally in contrast with normal unilateral extension in controls

• regenerating corticospinal tract axons after injury from mice injected with cre-expressing adenovirus are able to reform synaptic structures in the spinal cord caudal to the lesion site

reproductive system

increased prostate gland adenocarcinoma incidence ( J:144810 )

♂ • prostate adenocarcinoma is seen by 9-10 weeks of age in mutants infected with an adenovirus expressing Cre recombinase

increased prostate intraepithelial neoplasia incidence ( J:144810 )

♂ • mutants infected with an adenovirus expressing Cre recombinase develop PIN by 7 weeks of age

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:144810 )

♂ • prostate adenocarcinoma is seen by 9-10 weeks of age in mutants infected with an adenovirus expressing Cre recombinase

increased prostate intraepithelial neoplasia incidence ( J:144810 )

♂ • mutants infected with an adenovirus expressing Cre recombinase develop PIN by 7 weeks of age

Genotype
MGI:5503216

cn3

• Allelic Composition: Kdr^tm1Jrt/Kdr⁺; Pten^tm1Hwu/Pten^tm1Hwu; Twist2^{tm1.1(cre)Dor}/Twist2⁺
• Genetic Background: B6.129-Twist2^{tm1.1(cre)Dor} Kdr^tm1Jrt Pten^tm1Hwu

Defect in angioblast differentiation in Pten^tm1Hwu/Pten^tm1Hwu Kdr^tm1Jrt/Kdr⁺ Twist2^{tm1.1(cre)Dor}/Twist2⁺ mice

cardiovascular system

abnormal vasculogenesis ( J:192736 )

• vasculogenesis defect

• impaired differentiation of angioblasts into mature endothelial cells and blood vessels

respiratory system

abnormal lung morphology ( J:192736 )

• increase in angioblasts in E18.5 lungs

Genotype
MGI:5503192

cn4

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Twist2^{tm1.1(cre)Dor}/Twist2⁺
• Genetic Background: B6.129-Twist2^{tm1.1(cre)Dor} Pten^tm1Hwu

Increase in mesenchymal cell proliferation in Pten^tm1Hwu/Pten^tm1Hwu Twist2^{tm1.1(cre)Dor}/Twist2⁺ mice

mortality/aging

neonatal lethality, complete penetrance ( J:192736 )

• mutants with less severe phenotypes die within 2-3 hours of birth, displaying cyanosis, chest retractions, and dyspnea

lethality throughout fetal growth and development, incomplete penetrance ( J:192736 )

• lethality between E15.5 and E18.5

respiratory system

abnormal lung morphology ( J:192736 )

• increase in collagen deposition in the lungs

• alveolar spaces are frequently lined by cuboidal cells with immature lamellar bodies

abnormal lung vasculature morphology ( J:192736 )

• reduction in distal capillary network density in E15.5 lungs

• the capillary network is misaligned with corresponding respiratory airways (airway/capillary uncoupling or dysplasia) at E18.5

• increase in the distance between the capillaries and the lumen of the airways

abnormal lung development ( J:192736 )

• marker analysis indicates expansion of the distal epithelial progenitor cell domain

abnormal lung-associated mesenchyme development ( J:192736 )

• E18.5 lungs exhibit a hypercellular mesenchymal compartment

• more than 5-fold increase in the number of CD45-CD31+ embryonic mesenchymal progenitor side population (E-SP) and CD45-CD31- E-SP cell populations in E17.5 lungs indicating an increase in lung mesenchymal progenitor cell populations

respiratory distress ( J:192736 )

• in mutants with less severe phenotypes that die within hours of birth

cardiovascular system

abnormal lung vasculature morphology ( J:192736 )

• reduction in distal capillary network density in E15.5 lungs

• the capillary network is misaligned with corresponding respiratory airways (airway/capillary uncoupling or dysplasia) at E18.5

• increase in the distance between the capillaries and the lumen of the airways

abnormal vascular development ( J:192736 )

• 44% of embryos lack of vascularization in entire embryos at E15.5

• E15.5 embryos show lack of vascularization in organs such as limbs and liver

• impaired differentiation of angioblasts into mature endothelial cells and blood vessels

hemorrhage ( J:192736 )

• 15% of embryos exhibit hemorrhage at E18.5

homeostasis/metabolism

decreased blood oxygen capacity ( J:192736 )

• newborns show a decrease in blood oxygenation

cyanosis ( J:192736 )

• in mutants with less severe phenotypes that die within hours of birth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
persistent fetal circulation syndrome		DOID:13042	OMIM:265380	J:192736

Genotype
MGI:4839213

cn5

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Gdf9-icre)5092Coo/0
• Genetic Background: B6.Cg-Pten^tm1Hwu Tg(Gdf9-icre)5092Coo

cellular

abnormal oocyte morphology ( J:131827 )

♀ • accelerated oocyte growth

♀ • many transient follicles contain degraded oocytes

growth/size/body

enlarged ovary ( J:131827 )

♀ • at P8, ovaries appear larger with more activated follicles

♀ • by P23 and 35, ovaries remain larger and contain more activated follicles

endocrine/exocrine glands

abnormal corpus luteum morphology ( J:131827 )

♀ • luteolysis is observed (degeneration of corpora lutea) at 12 weeks of age

abnormal ovarian follicle morphology ( J:131827 )

♀ • at P8, ovaries appear larger with more activated follicles, including transient follicles containing enlarged oocytes surrounded by flattened pregranulosa cells, primary follicles with enlarged oocytes surrounded by one layer of cuboidal granulosa cells and some secondary follicles with two layers of granulosa cells

♀ • follicular structure at 12 weeks of age is deformed and luteolysis is observed

♀ • reduction in follicle death and clearance before and around the time of sexual maturity

♀ • at 7 weeks of age, ovaries show increased numbers of transient and preantral type 5 follicles

abnormal ovarian folliculogenesis ( J:131827 )

♀ • growth dynamics of activated transient follicles is different than in controls, with some follicles remaining at the transient stage whereas others develop further

abnormal primordial ovarian follicle morphology ( J:131827 )

♀ • premature activation of the primordial follicle pool resulting in depletion of primordial follicles in early adulthood

decreased primordial ovarian follicle number ( J:131827 )

♀ • percentage of primordial follicles in ovaries at P8 is lower (49.6%) than in controls (83.6%)

absent primordial ovarian follicles ( J:131827 )

♀ • by P23, no primordial follicles can be identified in mutants compared to 69.2% of follicles in controls areas are still at the primordial stage

enlarged ovary ( J:131827 )

♀ • at P8, ovaries appear larger with more activated follicles

♀ • by P23 and 35, ovaries remain larger and contain more activated follicles

premature ovarian failure ( J:131827 )

♀ • females exhibit activation of the pool of primordial follicles that leads to follicle depletion, causing premature ovarian failure

♀ • many transient follicles contain degraded oocytes suggesting that some prematurely activated follicles undergo atresia

homeostasis/metabolism

increased follicle stimulating hormone level ( J:131827 )

• increase in levels of follicle-stimulating hormone at 12-20-week old females

increased luteinizing hormone level ( J:131827 )

• increase in levels of luteinizing hormone at 12-20-week old females

mortality/aging

premature ovarian failure ( J:131827 )

♀ • females exhibit activation of the pool of primordial follicles that leads to follicle depletion, causing premature ovarian failure

♀ • many transient follicles contain degraded oocytes suggesting that some prematurely activated follicles undergo atresia

reproductive system

abnormal oocyte morphology ( J:131827 )

♀ • accelerated oocyte growth

♀ • many transient follicles contain degraded oocytes

abnormal corpus luteum morphology ( J:131827 )

♀ • luteolysis is observed (degeneration of corpora lutea) at 12 weeks of age

abnormal ovarian follicle morphology ( J:131827 )

♀ • at P8, ovaries appear larger with more activated follicles, including transient follicles containing enlarged oocytes surrounded by flattened pregranulosa cells, primary follicles with enlarged oocytes surrounded by one layer of cuboidal granulosa cells and some secondary follicles with two layers of granulosa cells

♀ • follicular structure at 12 weeks of age is deformed and luteolysis is observed

♀ • reduction in follicle death and clearance before and around the time of sexual maturity

♀ • at 7 weeks of age, ovaries show increased numbers of transient and preantral type 5 follicles

abnormal ovarian folliculogenesis ( J:131827 )

♀ • growth dynamics of activated transient follicles is different than in controls, with some follicles remaining at the transient stage whereas others develop further

abnormal primordial ovarian follicle morphology ( J:131827 )

♀ • premature activation of the primordial follicle pool resulting in depletion of primordial follicles in early adulthood

decreased primordial ovarian follicle number ( J:131827 )

♀ • percentage of primordial follicles in ovaries at P8 is lower (49.6%) than in controls (83.6%)

absent primordial ovarian follicles ( J:131827 )

♀ • by P23, no primordial follicles can be identified in mutants compared to 69.2% of follicles in controls areas are still at the primordial stage

enlarged ovary ( J:131827 )

♀ • at P8, ovaries appear larger with more activated follicles

♀ • by P23 and 35, ovaries remain larger and contain more activated follicles

premature ovarian failure ( J:131827 )

♀ • females exhibit activation of the pool of primordial follicles that leads to follicle depletion, causing premature ovarian failure

♀ • many transient follicles contain degraded oocytes suggesting that some prematurely activated follicles undergo atresia

abnormal estrous cycle ( J:131827 )

♀ • older females exhibit irregular estrous cycles

female infertility ( J:131827 )

♀ • females become infertile in early adulthood, after 12-13 weeks of age

Genotype
MGI:5517706

cn6

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: B6.Cg-Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:197590 )

• at P14, thyroid architecture is altered, with multilayered epithelial cells surrounding the colloid lumen and with some dysmorphic follicles containing abnormal material inside

abnormal thyroid follicle morphology ( J:197590 )

• dysmorphic follicles containing abnormal material inside and multiple degenerative follicles which have varying degrees of colloid depletion are seen at P14

enlarged thyroid gland ( J:197590 )

• increase in thyroid size is already seen at E15.5 and is striking by P14

thyroid gland hyperplasia ( J:197590 )

• increase in epithelial cell proliferation rate at E15.5 and P14

• Background Sensitivity: at P14, epithelial cell proliferation rates are higher on the congenic C57BL/6 background than on the BALB/c background

increased thyroid adenoma incidence ( J:197590 )

• at P14, thyroid structure is completely altered with multiple degenerative follicles, which have varying degrees of colloid depletion, resembling a follicular adenoma

homeostasis/metabolism

decreased thyroxine level ( J:197590 )

• decrease in T4 hormonal levels at P14

increased thyroid-stimulating hormone level ( J:197590 )

• increase in TSH at P14

mortality/aging

postnatal lethality, complete penetrance ( J:197590 )

• all mutants die before 2 weeks of age due to compression of the trachea and esophagus by the enlarged thyroid

neoplasm

increased thyroid adenoma incidence ( J:197590 )

• at P14, thyroid structure is completely altered with multiple degenerative follicles, which have varying degrees of colloid depletion, resembling a follicular adenoma

Genotype
MGI:5517709

cn7

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: B6.Cg-Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:197590 )

• altered thyroid structure with normal areas that include colloid-filled follicles and normal areas with focal hyperplasia, polynuclear cells, small nonencapsulated areas of hypercellularity with solid and/or mircofollicular patterns and internal hemorrhage

increased thyroid tumor incidence ( J:197590 )

• 100% of mutants develop differentiated follicular tumors of the thyroid after about 2 years of age

homeostasis/metabolism

decreased thyroxine level ( J:197590 )

• P14 mutants show a mild decrease of T4 but normal TSH

neoplasm

increased thyroid tumor incidence ( J:197590 )

• 100% of mutants develop differentiated follicular tumors of the thyroid after about 2 years of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
follicular thyroid carcinoma		DOID:3962	OMIM:188470	J:197590

Genotype
MGI:4882033

cn8

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Tyr-cre)1Lru/0
• Genetic Background: B6.Cg-Pten^tm1Hwu Tg(Tyr-cre)1Lru

Smaller body size of Pten^tm1Hwu/Pten^tm1Hwu Tg(Tyr-cre)1Lru/0 (HM) mice at P20

mortality/aging

postnatal lethality, complete penetrance ( J:155110 )

• die between 13 and 20 days after birth

growth/size/body

slow postnatal weight gain ( J:155110 )

• although mutants are similar in weight and size as wild-type mice on P2, they fail to gain as much weight over the next 20 days as controls

digestive/alimentary system

abnormal intestine morphology ( J:155110 )

• mutants exhibit some intraluminal bubbles along the gastrointestinal tract

• mutants exhibit intestinal pseudoobstruction

distended cecum ( J:155110 )

• dilatation of the cecum

abnormal digestion ( J:155110 )

• mutants exhibit intestinal pseudoobstruction

nervous system

abnormal enteric nervous system morphology ( J:155110 )

• hypertrophy and hyperplasia of the myenteric and submucosal plexus in the enteric nervous system by 2 weeks of age resulting in ganglioneuromatosis

abnormal enteric ganglia morphology ( J:155110 )

• enteric ganglia are bigger than in wild-type at P15

abnormal enteric neuron morphology ( J:155110 )

• hyperplasia is observed in enteric neuronal cells at E17.5 while hypertrophy of enteric neuronal cells is only seen after birth and not during embryonic development

pigmentation

hyperpigmentation ( J:155110 )

• hyperpigmentation in the tail, pinna, paws, skin, and olfactory bulb

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intestinal pseudo-obstruction		DOID:0080072		J:155110

Genotype
MGI:4882031

cn9

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Zp3-cre)93Knw/0
• Genetic Background: B6.Cg-Pten^tm1Hwu Tg(Zp3-cre)93Knw

reproductive system

reproductive system phenotype ( J:151696 )

N • mice exhibit normal follicular development, showing healthy corpora lutea and preovulatory follicles at 16 weeks of age, normal resumption of meiosis, ovulation, fertilization and fertility, although PI3K-Akt signaling is elevated

Genotype
MGI:5787929

cn10

• Allelic Composition: Nf1^tm1Fcr/Nf1⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Mx1-cre)1Cgn/0
• Genetic Background: B6.Cg-Tg(Mx1-cre)1Cgn Nf1^tm1Fcr Pten^tm1Hwu

mortality/aging

premature death ( J:232645 )

• mice injected intraperitoneally with poly(I:C) at P8 to induce loss of Pten all die at 20 to 35 days of age

hematopoietic system

abnormal hemopoiesis ( J:232645 )

• mice injected with poly(I:C) at P8 develop myeloproliferative neoplasm with clinical manifestations of Juvenile myelomonocytic leukemia at 2-3 weeks post induction

anemia ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit anemia 2-3 weeks post induction

decreased bone marrow cell number ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit reduced total cell numbers in bone marrow at 2-3 weeks post induction

decreased hemoglobin content ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit decreased hemoglobin 2-3 weeks post induction

thrombocytosis ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased platelets 2-3 weeks post induction

decreased lymphocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show a reduction in lymphocytes 2-3 weeks post induction

decreased B cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased B-cell (CD19+) populations in PB and spleen at 2-3 weeks post induction

decreased T cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased T-cell (CD3e+) populations in PB and spleen at 2-3 weeks post induction

increased leukocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit a modest elevation in white blood cells 2-3 weeks post poly(I:C) treatment

increased granulocyte number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in granulocytes in bone marrow, blood, and spleen 2-3 weeks post induction

increased macrophage cell number ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased macrophages in bone marrow, blood, and spleen at 2-3 weeks post induction

increased monocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in monocytes in bone marrow, blood, and spleen 2-3 weeks post induction

abnormal hematopoietic stem cell morphology ( J:232645 )

• bone marrow of mice injected with poly(I:C) at P8 shows decreased hematopoietic progenitor cells, including LIN-, LIN-Sca1-1-, cKit+, and LIN-Sca1-1+cKit+, are decreased, with less apoptosis

• spleen of mice injected with poly(I:C) at P8 shows an increase in hematopoietic progenitor cells

abnormal spleen morphology ( J:232645 )

• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage and granulocyte infiltration in the spleen at 2-3 weeks post induction

• spleen of mice injected with poly(I:C) at P8 shows an increase in hematopoietic progenitor cells

enlarged spleen ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen size

increased spleen weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen weight

immune system

decreased lymphocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show a reduction in lymphocytes 2-3 weeks post induction

decreased B cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased B-cell (CD19+) populations in PB and spleen at 2-3 weeks post induction

decreased T cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased T-cell (CD3e+) populations in PB and spleen at 2-3 weeks post induction

increased leukocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit a modest elevation in white blood cells 2-3 weeks post poly(I:C) treatment

increased granulocyte number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in granulocytes in bone marrow, blood, and spleen 2-3 weeks post induction

increased macrophage cell number ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased macrophages in bone marrow, blood, and spleen at 2-3 weeks post induction

increased monocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in monocytes in bone marrow, blood, and spleen 2-3 weeks post induction

abnormal spleen morphology ( J:232645 )

• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage and granulocyte infiltration in the spleen at 2-3 weeks post induction

• spleen of mice injected with poly(I:C) at P8 shows an increase in hematopoietic progenitor cells

enlarged spleen ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen size

increased spleen weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen weight

liver/biliary system

abnormal liver morphology ( J:232645 )

• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage infiltration in the liver at 2-3 weeks post induction

enlarged liver ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased liver size

increased liver weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased liver weight

neoplasm

increased tumor incidence ( J:232645 )

• mice injected with poly(I:C) at P8 develop myeloproliferative neoplasm with clinical manifestations of Juvenile myelomonocytic leukemia at 2-3 weeks post induction

• recipient mice transplanted with bone marrow nucleated cells from mutants develop an indolent myelodysplastic syndrome or myeloproliferative neoplasm by 8 weeks posttransplantation

• mice injected with poly(I:C) at 6 weeks of age develop a transient myeloproliferative neoplasm after 3 weeks post induction and 1/7 transform to T-ALL

increased T cell acute lymphoblastic leukemia incidence ( J:232645 )

• mice injected with poly(I:C) at 6 weeks of age develop a transient myeloproliferative neoplasm after 3 weeks post induction and 1/7 transform to T-ALL

respiratory system

abnormal lung morphology ( J:232645 )

• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage infiltration in the spleens, livers, and lungs at 2-3 weeks post induction

skeleton

abnormal bone marrow morphology ( J:232645 )

• mice injected with poly(I:C) at P8 show increases in monocytes/macrophages and granulocytes in the bone marrow at 2-3 weeks post induction

• bone marrow of mice injected with poly(I:C) at P8 shows decreased hematopoietic progenitor cells, including LIN-, LIN-Sca1-1-, cKit+, and LIN-Sca1-1+cKit+, are decreased, with less apoptosis

growth/size/body

enlarged liver ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased liver size

increased liver weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased liver weight

enlarged spleen ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen size

increased spleen weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
juvenile myelomonocytic leukemia		DOID:0050458	OMIM:607785	J:232645

Genotype
MGI:5787932

cn11

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Mx1-cre)1Cgn/0
• Genetic Background: B6.Cg-Tg(Mx1-cre)1Cgn Pten^tm1Hwu

mortality/aging

premature death ( J:232645 )

• median survival of poly(I:C) injected mice at P8 is 35 days

hematopoietic system

enlarged spleen ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen size

increased spleen weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen weight

anemia ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit anemia 2-3 weeks post induction

increased granulocyte number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in granulocytes 2-3 weeks post induction

thrombocytosis ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased platelets 2-3 weeks post induction, although the level of platelet increase in smaller than in mice also heterozygous for Nf1^tm1Fcr

decreased lymphocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show a reduction in lymphocytes 2-3 weeks post induction

decreased B cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased B-cell (CD19+) populations in PB and spleen at 2-3 weeks post induction

decreased T cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased T-cell (CD3e+) populations in PB and spleen at 2-3 weeks post induction

increased macrophage cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show substantial macrophage infiltration in the spleens, livers, and lungs at 2-3 weeks post induction

increased monocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in monocytes in the spleens, livers, and lungs at 2-3 weeks post induction

immune system

enlarged spleen ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen size

increased spleen weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen weight

increased granulocyte number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in granulocytes 2-3 weeks post induction

decreased lymphocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show a reduction in lymphocytes 2-3 weeks post induction

decreased B cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased B-cell (CD19+) populations in PB and spleen at 2-3 weeks post induction

decreased T cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased T-cell (CD3e+) populations in PB and spleen at 2-3 weeks post induction

increased macrophage cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show substantial macrophage infiltration in the spleens, livers, and lungs at 2-3 weeks post induction

increased monocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in monocytes in the spleens, livers, and lungs at 2-3 weeks post induction

liver/biliary system

abnormal liver size ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased liver size

increased liver weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased liver weight

neoplasm

increased tumor incidence ( J:232645 )

• mice injected with poly(I:C) at 6 weeks of age develop a transient myeloproliferative neoplasm after 3 weeks post induction and 5/7 transform to T-ALL

increased T cell acute lymphoblastic leukemia incidence ( J:232645 )

• mice injected with poly(I:C) at 6 weeks of age develop a transient myeloproliferative neoplasm after 3 weeks post induction and 5/7 transform to T-ALL

growth/size/body

increased liver weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased liver weight

enlarged spleen ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen size

increased spleen weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen weight

Genotype
MGI:5902387

cn12

• Allelic Composition: Cnp^tm1(cre)Kan/Cnp⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: B6N.129-Cnp^tm1(cre)Kan Pten^tm1Hwu

nervous system

tomacula ( J:236408 )

♂

Genotype
MGI:5013604

cn13

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Cop1^tm2.1Vmd/Cop1^tm2.1Vmd; Tg(Pbsn-cre)4Prb/0
• Genetic Background: B6N.CgCop1^tm2.1Vmd Pten^tm1Hwu Tg(Pbsn-cre)4Prb

neoplasm

increased prostate gland adenocarcinoma incidence ( J:172653 )

♂ • invasive in 11 of 13 mice at 30 weeks of age

increased prostate intraepithelial neoplasia incidence ( J:172653 )

♂ • high grade in 2 of 13 mice at 30 weeks of age

reproductive system

increased prostate gland adenocarcinoma incidence ( J:172653 )

♂ • invasive in 11 of 13 mice at 30 weeks of age

increased prostate intraepithelial neoplasia incidence ( J:172653 )

♂ • high grade in 2 of 13 mice at 30 weeks of age

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:172653 )

♂ • invasive in 11 of 13 mice at 30 weeks of age

increased prostate intraepithelial neoplasia incidence ( J:172653 )

♂ • high grade in 2 of 13 mice at 30 weeks of age

Genotype
MGI:4839500

cn14

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Mx1-cre)1Cgn/0
• Genetic Background: BKS.Cg-Ptprc^b Thy1^a Tg(Mx1-cre)1Cgn Pten^tm1Hwu

mortality/aging

premature death ( J:109085 )

• mutants become ill shortly after pIpC treatment and exhibit lethargy, ruffling of fur, and hunched posture and die from leukemia

hematopoietic system

enlarged thymus ( J:109085 )

• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus

spleen hyperplasia ( J:109085 )

• 10-fold increase in spleen cellularity after pIpC administration to induce Cre expression

abnormal blood cell morphology/development ( J:109085 )

• increase in blast cell frequency after pIpC administration to induce Cre expression

extramedullary hematopoiesis ( J:109085 )

• mice treated with polyinosine-polycytidine (pIpC) to induce Cre expression exhibit extramedullary hematopoiesis, with prominent expansion in the number of immature myeloid cells

• mice develop myeloproliferative disease shortly after pIpC administration to induce Cre expression with complete effacement of the splenic architecture

decreased bone marrow cell number ( J:109085 )

• reduction in bone marrow cellularity after pIpC administration to induce Cre expression

abnormal hematopoietic stem cell physiology ( J:109085 )

• mice treated with pIpC to induce Cre expression exhibit an increase in hematopoietic stem cell proliferation but become depleted, most likely due to inhibition of self-renewal as no increase in cell death was observed

• mutants maintained on rapamycin after pIpC treatment do not exhibit expansion of hematopoietic stem cells

immune system

enlarged thymus ( J:109085 )

• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus

spleen hyperplasia ( J:109085 )

• 10-fold increase in spleen cellularity after pIpC administration to induce Cre expression

neoplasm

increased leukemia incidence ( J:109085 )

• within 4-6 weeks after pIpC treatment, most mutants progress to leukemia, including acute myeloid leukemia and acute lymphoblastic leukemia

• mutants maintained on rapamycin after pIpC treatment do not develop leukemia

increased acute lymphoblastic leukemia incidence ( J:109085 )

• seen in mutants within 4-6 weeks after pIpC treatment

increased acute promyelocytic leukemia incidence ( J:109085 )

• seen in mutants within 4-6 weeks after pIpC treatment

endocrine/exocrine glands

enlarged thymus ( J:109085 )

• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus

growth/size/body

spleen hyperplasia ( J:109085 )

• 10-fold increase in spleen cellularity after pIpC administration to induce Cre expression

Genotype
MGI:5506907

cn15

• Allelic Composition: Pik3ca^tm1Jjz/Pik3ca^tm1Jjz; Pik3cb^tm1Jjz/Pik3cb^tm1Jjz; Pten^tm1Hwu/Pten^tm1Hwu; Tg(KRT14-cre)#Smr/0
• Genetic Background: FVB.Cg-Pik3ca^tm1Jjz Pik3cb^tm1Jjz Pten^tm1Hwu Tg(KRT14-cre)#Smr

integument

integument phenotype ( J:199362 )

N • mutants do not develop hamartomas over a period of 300 days and epidermal thickness is normal at 8 weeks of age

Genotype
MGI:5506905

cn16

• Allelic Composition: Pik3ca^tm1Jjz/Pik3ca^tm1Jjz; Pten^tm1Hwu/Pten^tm1Hwu; Tg(KRT14-cre)#Smr/0
• Genetic Background: FVB.Cg-Pik3ca^tm1Jjz Pten^tm1Hwu Tg(KRT14-cre)#Smr

integument

thick epidermis stratum basale ( J:199362 )

• expanded basal cell layers

skin lesions ( J:199362 )

• development of skin lesions is delayed and severity is reduced compared to single Pten mutants

thick skin ( J:199362 )

• skin is thickened at 8 weeks of age, but to a lesser extent than in single Pten mutants

increased skin hamartoma incidence ( J:199362 )

• develop skin hamartomas with a median latency of 121 days

neoplasm

increased skin hamartoma incidence ( J:199362 )

• develop skin hamartomas with a median latency of 121 days

Genotype
MGI:5506906

cn17

• Allelic Composition: Pik3cb^tm1Jjz/Pik3cb^tm1Jjz; Pten^tm1Hwu/Pten^tm1Hwu; Tg(KRT14-cre)#Smr/0
• Genetic Background: FVB.Cg-Pik3cb^tm1Jjz Pten^tm1Hwu Tg(KRT14-cre)#Smr

integument

abnormal epidermis suprabasal layer morphology ( J:199362 )

• accumulation of terminally differentiated suprabasal cells

skin lesions ( J:199362 )

• development of skin lesions is delayed and severity is reduced compared to single Pten mutants

thick skin ( J:199362 )

• skin is thickened at 8 weeks of age, but to a lesser extent than in single Pten mutants

increased skin hamartoma incidence ( J:199362 )

• develop skin hamartomas with a median latency of 131 days

neoplasm

increased skin hamartoma incidence ( J:199362 )

• develop skin hamartomas with a median latency of 131 days

Genotype
MGI:5506904

cn18

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(KRT14-cre)#Smr/0
• Genetic Background: FVB.Cg-Pten^tm1Hwu Tg(KRT14-cre)#Smr

integument

abnormal epidermal layer morphology ( J:199362 )

• marker analysis indicates a perturbed basal-to-suprabasal transition

hyperkeratosis ( J:199362 )

thick epidermis suprabasal layer ( J:199362 )

• expanded suprabasal layer as indicated by an increase in Keratin 10-postive cells

thick epidermis ( J:199362 )

• increase in the number of epidermal cell layers at 8 weeks of age

skin lesions ( J:199362 )

• progressive development of multiple dermal lesions after weaning

thick skin ( J:199362 )

• at 8 weeks of age

increased skin hamartoma incidence ( J:199362 )

• multiple cutaneous hamartomas are seen all over the body within 12 weeks of age

• median onset of disease is 62 days

• mice treated with BKM120, a pan-class I PI3K inhibitor, beginning at 3 weeks of age, do not develop PTEN hamartoma tumor syndrome skin lesions; removal of BKM120 results in development of lesions, indicating that continuous treatment is required

• mice with advanced multiple skin hamartomas treated with BKM120 show improved skin conditions

increased skin papilloma incidence ( J:199362 )

• papillomatous lesions around the facial orifices, ears, and paws, with most associated with hyperkeratosis

neoplasm

increased skin hamartoma incidence ( J:199362 )

• multiple cutaneous hamartomas are seen all over the body within 12 weeks of age

• median onset of disease is 62 days

• mice treated with BKM120, a pan-class I PI3K inhibitor, beginning at 3 weeks of age, do not develop PTEN hamartoma tumor syndrome skin lesions; removal of BKM120 results in development of lesions, indicating that continuous treatment is required

• mice with advanced multiple skin hamartomas treated with BKM120 show improved skin conditions

increased skin papilloma incidence ( J:199362 )

• papillomatous lesions around the facial orifices, ears, and paws, with most associated with hyperkeratosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cowden syndrome		DOID:6457	OMIM:PS158350	J:199362

Genotype
MGI:5460854

cn19

• Allelic Composition: Calca^{tm1.1(cre/ERT2)Ptch}/Calca⁺; Trp53^tm1Brn/Trp53^tm1Brn; Rb1^tm2Brn/Rb1^tm2Brn; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129 * 129P2/OlaHsd * 129S4/SvJae * BALB/c * FVB/N

mortality/aging

postnatal lethality ( J:190366 )

• death within 3 months of tamoxifen treatment

respiratory system

increased lung small cell carcinoma incidence ( J:190366 )

• small cell lung tumors 2.5 months after tamoxifen treatment

abnormal pulmonary neuroendocrine body morphology ( J:190366 )

• increased proliferation of pulmonary neuroendocrine cells

neoplasm

increased thyroid tumor incidence ( J:190366 )

• all mice develop thyroid tumors

increased metastatic potential ( J:190366 )

• increased invasiveness at 2.5 months after tamoxifen treatment

increased lung small cell carcinoma incidence ( J:190366 )

• small cell lung tumors 2.5 months after tamoxifen treatment

endocrine/exocrine glands

increased thyroid tumor incidence ( J:190366 )

• all mice develop thyroid tumors

Genotype
MGI:4847601

cn20

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129 * 129S4/SvJae * BALB/c * C57BL/6

mortality/aging

decreased tumor-free survival time ( J:130367 )

• most females that develop lymphomas die at about 9 weeks post-4OHT injection

• all mutants die from tumor burden by 45 weeks post-4OHT injection

neoplasm

increased tumor incidence ( J:130367 )

• treatment of mice with 4OHT at 6 weeks of age to induce cre-mediated recombination results in tumor formation with a mean latency of 17 weeks

• multiple tumors are seen in 27.3% of 4OHT-treated mice

• 46.1% of females develop endometrial cancer after 4OHT treatment

increased gastrointestinal tumor incidence ( J:130367 )

♂ • 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine

increased T cell derived lymphoma incidence ( J:130367 )

• 76.9% incidence of lymphomas in females after 4OHT treatment

• 40% incidence of lymphomas in males after 4OHT treatment

• lymphomas mainly arise from the thymus and mesenteric lymph nodes

• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts

increased prostate gland tumor incidence ( J:130367 )

♂ • 20% of males develop prostate cancer after 4OHT treatment

increased prostate intraepithelial neoplasia incidence ( J:130367 )

♂ • prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment

increased incidence of tumors by chemical induction ( J:130367 )

• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively

increased skin squamous cell carcinoma incidence ( J:130367 )

• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment

digestive/alimentary system

intestine polyps ( J:130367 )

• males develop small or large intestinal polyps at more than 35 weeks post 4OHT treatment

increased gastrointestinal tumor incidence ( J:130367 )

♂ • 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:130367 )

• 76.9% incidence of lymphomas in females after 4OHT treatment

• 40% incidence of lymphomas in males after 4OHT treatment

• lymphomas mainly arise from the thymus and mesenteric lymph nodes

• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts

prostate gland hyperplasia ( J:130367 )

♂ • prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment

increased prostate gland tumor incidence ( J:130367 )

♂ • 20% of males develop prostate cancer after 4OHT treatment

increased prostate intraepithelial neoplasia incidence ( J:130367 )

♂ • prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment

reproductive system

prostate gland hyperplasia ( J:130367 )

♂ • prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment

increased prostate gland tumor incidence ( J:130367 )

♂ • 20% of males develop prostate cancer after 4OHT treatment

increased prostate intraepithelial neoplasia incidence ( J:130367 )

♂ • prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment

endometrium hyperplasia ( J:130367 )

♀ • most females develop endometrial hyperplasia at between 7 and 9 weeks post 4-OHT treatment

integument

increased skin squamous cell carcinoma incidence ( J:130367 )

• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:130367 )

• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively

immune system

increased T cell derived lymphoma incidence ( J:130367 )

• 76.9% incidence of lymphomas in females after 4OHT treatment

• 40% incidence of lymphomas in males after 4OHT treatment

• lymphomas mainly arise from the thymus and mesenteric lymph nodes

• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts

hematopoietic system

increased T cell derived lymphoma incidence ( J:130367 )

• 76.9% incidence of lymphomas in females after 4OHT treatment

• 40% incidence of lymphomas in males after 4OHT treatment

• lymphomas mainly arise from the thymus and mesenteric lymph nodes

• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts

Genotype
MGI:5487550

cn21

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tgfbr1^tm1.1Karl/Tgfbr1^tm1.1Karl; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6 * CD-1 * FVB/N

Tgfbr1^tm1.1Karl/Tgfbr1^tm1.1Karl Pten^tm1Hwu/Pten^tm1Hwu Tg(KRT14-cre/ERT)20Efu/0 mice develop anal squamous cell carcinoma

neoplasm

increased squamous cell carcinoma incidence ( J:194652 , J:209026 )

• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck tumors; papillomas progress to squamous cell carcinoma in the head and neck and oral cavity (J:194652)

• treatment with rapamycin 2 weeks after tamoxifen administration delays initiation and reduces progression of papilloma and onset of squamous cell carcinoma (J:194652)

• rapamycin treatment of mice with already established head and neck squamous cell carcinoma results in regression of those tumors; rapamycin decreases cell proliferation and increases apoptosis in these tumors (J:194652)

• anal neoplasms that develop in tamoxifen treated mice originate from squamous epithelia and not from columnar epithelia, indicating squamous cell carcinoma (J:209026)

• invasion into adjacent muscle tissue is seen in some mice (J:209026)

• anal squamous cell carcinoma shows increased levels of proinflammatory cytokines (J:209026)

• all mice develop head and neck squamous cell carcinomas 16 weeks after tamoxifen induction (J:209026)

• rapamycin treatment 2 weeks after tamoxifen administration decreases cell proliferation, and delays and reduces the progression of anal squamous cell carcinoma (J:209026)

increased papilloma incidence ( J:194652 )

• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck and oral cavity papillomas that progress to squamous cell carcinoma

increased organ/body region tumor incidence ( J:209026 )

• 33% of mice develop visible anal tumors in 6 weeks after tamoxifen treatment

increased oral papilloma incidence ( J:194652 )

digestive/alimentary system

increased oral papilloma incidence ( J:194652 )

abnormal anal canal morphology ( J:209026 )

• 4 weeks after oral tamoxifen treatment for 5 consecutive days, hyperplasia is seen in the perianal areas

growth/size/body

increased oral papilloma incidence ( J:194652 )

craniofacial

increased oral papilloma incidence ( J:194652 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
anal canal carcinoma		DOID:6126	OMIM:105580	J:209026
head and neck squamous cell carcinoma		DOID:5520	OMIM:275355	J:194652

Genotype
MGI:4943512

cn22

• Allelic Composition: Hspa5^tm1Alee/Hspa5^tm1.1Alee; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)4Prb/?
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2

neoplasm

neoplasm ( J:142106 )

N • mice do not develop detectable cancerous or precancerous lesions in the prostate

Genotype
MGI:3805865

cn23

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2

neoplasm

increased prostate gland tumor incidence ( J:142106 )

♂ • mutants develop tumors between 12 to 20 weeks, with 100% penetrance at 20 weeks

increased prostate gland adenocarcinoma incidence ( J:142106 )

♂ • all mice develop invasive adenocarcinoma in all prostate lobes

♂ • malignant cells invade through the basement membrane into the adjacent stroma, inducing both an inflammatory and a desmoplastic response, resulting in growth of fibrous and connective tissue around the tumor

increased prostate intraepithelial neoplasia incidence ( J:138565 )

♂ • mice develop prostate intraepithelial neoplasias

reproductive system

increased prostate gland tumor incidence ( J:142106 )

♂ • mutants develop tumors between 12 to 20 weeks, with 100% penetrance at 20 weeks

increased prostate gland adenocarcinoma incidence ( J:142106 )

♂ • all mice develop invasive adenocarcinoma in all prostate lobes

♂ • malignant cells invade through the basement membrane into the adjacent stroma, inducing both an inflammatory and a desmoplastic response, resulting in growth of fibrous and connective tissue around the tumor

increased prostate intraepithelial neoplasia incidence ( J:138565 )

♂ • mice develop prostate intraepithelial neoplasias

female infertility ( J:142106 )

♀

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:142106 )

♂ • mutants develop tumors between 12 to 20 weeks, with 100% penetrance at 20 weeks

increased prostate gland adenocarcinoma incidence ( J:142106 )

♂ • all mice develop invasive adenocarcinoma in all prostate lobes

♂ • malignant cells invade through the basement membrane into the adjacent stroma, inducing both an inflammatory and a desmoplastic response, resulting in growth of fibrous and connective tissue around the tumor

increased prostate intraepithelial neoplasia incidence ( J:138565 )

♂ • mice develop prostate intraepithelial neoplasias

Genotype
MGI:4943514

cn24

• Allelic Composition: Hspa5^tm1Alee/Hspa5⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)4Prb/?
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2

neoplasm

increased prostate gland adenocarcinoma incidence ( J:142106 )

♂ • mutants exhibit visible solid tumor mass with invasive adenocarcinoma in the anterior prostate, while the dorsolateral prostate and ventral prostate lobes keep their ductual structure, albeit with enlarged ducts

increased prostate intraepithelial neoplasia incidence ( J:142106 )

♂ • dorsolateral prostate and ventral prostate exhibit diffusive prostate intraepithelial neoplasia (PIN) with intact basement membrane

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:142106 )

♂ • mutants exhibit visible solid tumor mass with invasive adenocarcinoma in the anterior prostate, while the dorsolateral prostate and ventral prostate lobes keep their ductual structure, albeit with enlarged ducts

increased prostate intraepithelial neoplasia incidence ( J:142106 )

♂ • dorsolateral prostate and ventral prostate exhibit diffusive prostate intraepithelial neoplasia (PIN) with intact basement membrane

reproductive system

increased prostate gland adenocarcinoma incidence ( J:142106 )

♂ • mutants exhibit visible solid tumor mass with invasive adenocarcinoma in the anterior prostate, while the dorsolateral prostate and ventral prostate lobes keep their ductual structure, albeit with enlarged ducts

increased prostate intraepithelial neoplasia incidence ( J:142106 )

♂ • dorsolateral prostate and ventral prostate exhibit diffusive prostate intraepithelial neoplasia (PIN) with intact basement membrane

Genotype
MGI:4943513

cn25

• Allelic Composition: Hspa5^tm1Alee/Hspa5^tm1Alee; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)4Prb/?
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2

neoplasm

neoplasm ( J:142106 )

N • mice do not develop detectable cancerous or precancerous lesions in the prostate

Genotype
MGI:4882116

cn26

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(SFTPC-rtTA)5Jaw/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6 * FVB/N

respiratory system

abnormal respiratory epithelium morphology ( J:146355 )

• doxycyline treated mice exhibit an increase in proliferation of epithelial cells lining conducting airways

abnormal lung epithelium morphology ( J:146355 )

• papillary epithelial hyperplasia is seen as early as 4-6 weeks of age in mice treated with doxycycline

• papillary epithelial hyperplasia is characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protrude into the airway lumens

increased club cell number ( J:146355 )

• doxycyline treated mice exhibit an increase in proliferation of nonciliated bronchial and bronchiolar Clara cells

bronchiolar epithelial hyperplasia ( J:146355 )

• mice treated with doxycycline exhibit bronchiolar epithelial hyperplasia, producing papillae composed of fibrovascular cores lined by a hypercellular epithelium protruding into the airway lumens consisting of enlarged cells

bronchial epithelial hyperplasia ( J:146355 )

• mice treated with doxycycline exhibit bronchial epithelial hyperplasia, producing papillae composed of fibrovascular cores lined by a hypercellular epithelium protruding into the airway lumens consisting of enlarged cells

endocrine/exocrine glands

increased solitary pulmonary neuroendocrine cell number ( J:146355 )

• pulmonary neuroepithelial cell hyperplasia, with a 2-fold increase in the number of pulmonary neuroendocrine cells in mice treated with doxycycline

• however normal respiratory epithelial cell differentiation and respiratory epithelial cell polarity

nervous system

increased solitary pulmonary neuroendocrine cell number ( J:146355 )

• pulmonary neuroepithelial cell hyperplasia, with a 2-fold increase in the number of pulmonary neuroendocrine cells in mice treated with doxycycline

• however normal respiratory epithelial cell differentiation and respiratory epithelial cell polarity

neoplasm

neoplasm ( J:146355 )

N • overt pulmonary tumors are not observed in doxycycline treated mice at 6 weeks of age

Genotype
MGI:3813634

cn27

• Allelic Composition: Pgr^tm2(cre)Lyd/Pgr⁺; Pten^tm1Hwu/Pten^tm1Hwu; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

premature death ( J:139053 )

• impaired survival is seen beginning around 2 months of age

• death appears to result from excessive bleeding due to invasion of uterine blood vessels by tumor cells

reproductive system

increased endometrial carcinoma incidence ( J:139053 )

♀ • hyperplasia progresses to carcinoma by 3 weeks of age

endometrium hyperplasia ( J:139053 )

♀ • by P10, luminal and glandular epithelial hyperplasia are seen

enlarged uterus ( J:139053 )

♀ • enlarged relative to conditional mutants that are wild type for Trp53

neoplasm

increased endometrial carcinoma incidence ( J:139053 )

♀ • hyperplasia progresses to carcinoma by 3 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endometrial cancer		DOID:1380	OMIM:608089	J:139053

Genotype
MGI:6507866

cn28

• Allelic Composition: Igs2^{tm1(CAG-Met)Zsu}/Igs2⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2 * FVB/N

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:268934 )

♂ • mice develop prostatic sarcomatoid carcinoma

♂ • mice show a more aggressive prostatic tumor phenotype than single conditional Pten^tm1Hwu mice

increased prostate gland adenocarcinoma incidence ( J:268934 )

♂ • mice develop prostatic adenocarcinomas and invasive carcinomas

increased prostate intraepithelial neoplasia incidence ( J:268934 )

♂ • 5 of 5 mice develop multifocal high grade intraepithelial neoplasia (PIN) before 4 months of age

neoplasm

increased prostate gland tumor incidence ( J:268934 )

♂ • mice develop prostatic sarcomatoid carcinoma

♂ • mice show a more aggressive prostatic tumor phenotype than single conditional Pten^tm1Hwu mice

increased prostate gland adenocarcinoma incidence ( J:268934 )

♂ • mice develop prostatic adenocarcinomas and invasive carcinomas

increased prostate intraepithelial neoplasia incidence ( J:268934 )

♂ • 5 of 5 mice develop multifocal high grade intraepithelial neoplasia (PIN) before 4 months of age

increased metastatic potential ( J:268934 )

♂ • prostate cancer metastasis after 10 months of age with 62.5% of mice showing metastatic lesions

♂ • metastasis to lungs and periprostatic lymph nodes is seen

♂ • mice show an overall more invasive tumor phenotype than single conditional Pten^tm1Hwu mice

increased carcinoma incidence ( J:268934 )

♂ • 1 of 5 mice show invasive pancreatic carcinoma at 4-10 months and 6 of 8 mice develop invasive carcinoma after 10 months of age; 5 of 8 mice have invasive carcinoma with epithelial-mesenchymal transition and 5 of 8 mice have invasive carcinoma with metastasis

♂ • mice exhibit a transition from prostatic adenocarcinoma and invasive carcinoma lesions to pathology resembling prostatic sarcamoid carcinomas

♂ • sarcamoid carcinomas show spindle-like tumor cells, tumor cells with a multitude of mitotic figures, and haphazard acini and lobules of pleomorphic cells, indicating that these lesions possess mesenchymal morphology and proliferative and invasive features

reproductive system

increased prostate gland tumor incidence ( J:268934 )

♂ • mice develop prostatic sarcomatoid carcinoma

♂ • mice show a more aggressive prostatic tumor phenotype than single conditional Pten^tm1Hwu mice

increased prostate gland adenocarcinoma incidence ( J:268934 )

♂ • mice develop prostatic adenocarcinomas and invasive carcinomas

increased prostate intraepithelial neoplasia incidence ( J:268934 )

♂ • 5 of 5 mice develop multifocal high grade intraepithelial neoplasia (PIN) before 4 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:268934

Genotype
MGI:4829791

cn29

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

hematopoietic system

abnormal B cell negative selection ( J:155314 )

• bone marrow cultured with IL-7 over a 6 day period to promote selective expansion of pre-B cells exhibits an approximate 7-fold enhancement in the frequency of activated immature mutant B cells relative to immature wild-type B cells

• gating on activated B cells shows that immature mutant B cells proliferate to a much greater extent than immature wild-type B cells

• these experiments show that upon BCR engagement, immature B cells are activated and proliferate rather than being inhibited and undergoing anergy

increased B cell number ( J:83213 )

• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells

increased B-1 B cell number ( J:83213 )

• expansion of the B1 cell population

increased marginal zone B cell number ( J:83213 )

• expansion of the MZ B cell compartment

abnormal plasma cell morphology ( J:114881 )

• increase in numbers of IgM^hi antibody secreting cells and decrease in numbers of IgG^hi antibody secreting cells

decreased spleen germinal center number ( J:83213 )

• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens

abnormal B cell physiology ( J:83213 )

• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus

increased B cell apoptosis ( J:83213 )

• cultured B cells show increased apoptosis

increased B cell proliferation ( J:83213 , J:155314 )

• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor (J:83213)

• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages (J:83213)

• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2 (J:155314)

abnormal class switch recombination ( J:114881 )

• impaired class-switch recombination in antibody secreting cells in response to a T-dependent antigen; B cells fail to undergo class-switch recombination to IgG3 or IgG1 in the presence of LPS or LPS plus IL-4, respectively

• however, well-formed germinal centers are observed in spleen after immunization

decreased IgG level ( J:114881 )

• decrease in IgG after TNP-OVA immunization

increased IgM level ( J:114881 )

• increase in IgM after TNP-OVA immunization

immune system

abnormal B cell negative selection ( J:155314 )

• bone marrow cultured with IL-7 over a 6 day period to promote selective expansion of pre-B cells exhibits an approximate 7-fold enhancement in the frequency of activated immature mutant B cells relative to immature wild-type B cells

• gating on activated B cells shows that immature mutant B cells proliferate to a much greater extent than immature wild-type B cells

• these experiments show that upon BCR engagement, immature B cells are activated and proliferate rather than being inhibited and undergoing anergy

increased B cell number ( J:83213 )

• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells

increased B-1 B cell number ( J:83213 )

• expansion of the B1 cell population

increased marginal zone B cell number ( J:83213 )

• expansion of the MZ B cell compartment

abnormal plasma cell morphology ( J:114881 )

• increase in numbers of IgM^hi antibody secreting cells and decrease in numbers of IgG^hi antibody secreting cells

decreased spleen germinal center number ( J:83213 )

• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens

abnormal B cell physiology ( J:83213 )

• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus

increased B cell apoptosis ( J:83213 )

• cultured B cells show increased apoptosis

increased B cell proliferation ( J:83213 , J:155314 )

• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor (J:83213)

• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages (J:83213)

• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2 (J:155314)

abnormal class switch recombination ( J:114881 )

• impaired class-switch recombination in antibody secreting cells in response to a T-dependent antigen; B cells fail to undergo class-switch recombination to IgG3 or IgG1 in the presence of LPS or LPS plus IL-4, respectively

• however, well-formed germinal centers are observed in spleen after immunization

decreased IgG level ( J:114881 )

• decrease in IgG after TNP-OVA immunization

increased IgM level ( J:114881 )

• increase in IgM after TNP-OVA immunization

cellular

increased B cell apoptosis ( J:83213 )

• cultured B cells show increased apoptosis

increased B cell proliferation ( J:83213 , J:155314 )

• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor (J:83213)

• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages (J:83213)

• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2 (J:155314)

Genotype
MGI:4836609

cn30

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

immune system

abnormal macrophage chemotaxis ( J:148947 )

• macrophage recruitment to inflamed lungs is increased

abnormal alveolar macrophage morphology ( J:148947 )

• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type

abnormal neutrophil physiology ( J:114699 , J:145331 , J:148947 )

• neutrophils isolated from bone marrow live longer than wild-type neutrophils (J:114699)

• neutrophils exhibit enhanced ruffling in response to the chemoattractant fMLP or IL-8 (J:145331)

• polarized neutrophils exhibit a considerable increase in multiple pseudopodia compared to wild-type mice (J:145331)

• neutrophils show more diffuse F-actin localization at the leading edge or pseudopodia than wild-type neutrophils (J:145331)

• fMLP-stimulated, but not PMA-stimulated, neutrophils exhibit increased and prolonged superoxide production compared to wild-type neutrophils (J:145331)

• neutrophils exhibit enhanced transwell chemotaxis toward fMLP, IL-8 or C5a (J:145331)

• neutrophils are more active and move faster than wild-type neutrophils but lack some of the directionality of wild-type neutrophils (J:145331)

• in a model of peritonitis, neutrophil recruitment at sites of inflammation is increased in mutants compared to wild-type mice (J:145331)

• in a model of bacterial pneumonia, apoptosis of lung recruited neutrophils is reduced in mutants compared to wild-type mice (J:148947)

• neutrophils exhibit enhanced bacteria-killing capacity in a model of bacterial pneumonia (J:148947)

• neutrophils have an increased phagocytic index compared to wild-type in a model of bacterial pneumonia (J:148947)

• neutrophils exhibit enhanced E.coli and zymosan-induced phagocytosis-associated superoxide production (J:148947)

impaired neutrophil recruitment ( J:148947 )

• in a bacterial pneumonia model in which mutants are intratracheally infected with E.coli to induce lung inflammation, mutants exhibit an increase in bacteria-induced neutrophil recruitment compared to controls

• mutants treated with the chemotherapeutic drug, cyclophosphamide, to induce neutropenia, exhibit fewer neutrophils in the lungs than untreated mutants, but more neutrophils than drug treated wild-type mice

abnormal cytokine level ( J:148947 )

• increase in cytokine/chemokine concentrations in inflamed lungs of E.coli infected mutants due to increased numbers of resident alveolar macrophages and not due to enhanced capability of macrophages to produce cytokines or chemokines

lung inflammation ( J:148947 )

• mutants develop more severe lung inflammation in response to bacterial pneumonia than controls

decreased susceptibility to bacterial infection ( J:148947 )

• induction of neutropenia in mutants with the chemotherapeutic drug, cyclophosphamide, results in enhanced neutrophil accumulation in the lungs leading to better clearance of instilled bacteria and accelerated resolution of bacteria-induced lung inflammation

decreased susceptibility to bacterial infection induced morbidity/mortality ( J:148947 )

• mutants made neutropenic with the chemotherapeutic drug, cyclophosphamide, exhibit decreased mortality after E.coli challenge compared to wild-type mice due to enhanced neutrophil accumulation in the lungs (50% survival for mutants compared to 7% survival for wild-type mice)

increased susceptibility to bacterial infection ( J:148947 )

• mutants intratracheally infected with E.coli exhibit increased neutrophil recruitment to lungs and increased lung inflammation, pulmonary edema, and increased susceptibility to death compared to controls

increased susceptibility to bacterial infection induced morbidity/mortality ( J:148947 )

• mutants exhibit an increase in pneumonia-associated death rate compared to wild-type mice, with only 50% of mutants surviving compared to 80% survival of wild-type mice

hematopoietic system

abnormal macrophage chemotaxis ( J:148947 )

• macrophage recruitment to inflamed lungs is increased

abnormal alveolar macrophage morphology ( J:148947 )

• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type

abnormal neutrophil physiology ( J:114699 , J:145331 , J:148947 )

• neutrophils isolated from bone marrow live longer than wild-type neutrophils (J:114699)

• neutrophils exhibit enhanced ruffling in response to the chemoattractant fMLP or IL-8 (J:145331)

• polarized neutrophils exhibit a considerable increase in multiple pseudopodia compared to wild-type mice (J:145331)

• neutrophils show more diffuse F-actin localization at the leading edge or pseudopodia than wild-type neutrophils (J:145331)

• fMLP-stimulated, but not PMA-stimulated, neutrophils exhibit increased and prolonged superoxide production compared to wild-type neutrophils (J:145331)

• neutrophils exhibit enhanced transwell chemotaxis toward fMLP, IL-8 or C5a (J:145331)

• neutrophils are more active and move faster than wild-type neutrophils but lack some of the directionality of wild-type neutrophils (J:145331)

• in a model of peritonitis, neutrophil recruitment at sites of inflammation is increased in mutants compared to wild-type mice (J:145331)

• in a model of bacterial pneumonia, apoptosis of lung recruited neutrophils is reduced in mutants compared to wild-type mice (J:148947)

• neutrophils exhibit enhanced bacteria-killing capacity in a model of bacterial pneumonia (J:148947)

• neutrophils have an increased phagocytic index compared to wild-type in a model of bacterial pneumonia (J:148947)

• neutrophils exhibit enhanced E.coli and zymosan-induced phagocytosis-associated superoxide production (J:148947)

impaired neutrophil recruitment ( J:148947 )

• in a bacterial pneumonia model in which mutants are intratracheally infected with E.coli to induce lung inflammation, mutants exhibit an increase in bacteria-induced neutrophil recruitment compared to controls

• mutants treated with the chemotherapeutic drug, cyclophosphamide, to induce neutropenia, exhibit fewer neutrophils in the lungs than untreated mutants, but more neutrophils than drug treated wild-type mice

homeostasis/metabolism

pulmonary edema ( J:148947 )

• increased neutrophil recruitment to lungs leads to pulmonary edema formation and increased protein accumulation

abnormal cytokine level ( J:148947 )

• increase in cytokine/chemokine concentrations in inflamed lungs of E.coli infected mutants due to increased numbers of resident alveolar macrophages and not due to enhanced capability of macrophages to produce cytokines or chemokines

mortality/aging

decreased susceptibility to bacterial infection induced morbidity/mortality ( J:148947 )

• mutants made neutropenic with the chemotherapeutic drug, cyclophosphamide, exhibit decreased mortality after E.coli challenge compared to wild-type mice due to enhanced neutrophil accumulation in the lungs (50% survival for mutants compared to 7% survival for wild-type mice)

increased susceptibility to bacterial infection induced morbidity/mortality ( J:148947 )

• mutants exhibit an increase in pneumonia-associated death rate compared to wild-type mice, with only 50% of mutants surviving compared to 80% survival of wild-type mice

respiratory system

abnormal alveolar macrophage morphology ( J:148947 )

• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type

pulmonary edema ( J:148947 )

• increased neutrophil recruitment to lungs leads to pulmonary edema formation and increased protein accumulation

lung inflammation ( J:148947 )

• mutants develop more severe lung inflammation in response to bacterial pneumonia than controls

cellular

abnormal macrophage chemotaxis ( J:148947 )

• macrophage recruitment to inflamed lungs is increased

Genotype
MGI:5013951

cn31

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Inpp5d^tm1Rav/Inpp5d^tm1Rav; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

behavior/neurological

lethargy ( J:166155 )

• mutants exhibit lethargy by 4 months of age

hunched posture ( J:166155 )

• mutants exhibit a hunched posture by 4 months of age

growth/size/body

weight loss ( J:166155 )

• mutants exhibit weight loss by 4 months of age

enlarged spleen ( J:166155 )

• mutants exhibit splenomegaly by 4 months of age

hematopoietic system

enlarged spleen ( J:166155 )

• mutants exhibit splenomegaly by 4 months of age

abnormal B cell morphology ( J:166155 )

• CD19+ B cells are larger than B cells from wild-type mice

• B cell neoplasia

decreased B cell number ( J:166155 )

• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse

increased B cell number ( J:166155 )

• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease

abnormal myeloid leukocyte morphology ( J:166155 )

• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells

increased spleen white pulp amount ( J:166155 )

• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp

abnormal B cell physiology ( J:166155 )

• B cells exhibit enhanced survival

increased B cell proliferation ( J:166155 )

• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not

• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice

immune system

enlarged spleen ( J:166155 )

• mutants exhibit splenomegaly by 4 months of age

abnormal B cell morphology ( J:166155 )

• CD19+ B cells are larger than B cells from wild-type mice

• B cell neoplasia

decreased B cell number ( J:166155 )

• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse

increased B cell number ( J:166155 )

• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease

abnormal myeloid leukocyte morphology ( J:166155 )

• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells

increased spleen white pulp amount ( J:166155 )

• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp

abnormal B cell physiology ( J:166155 )

• B cells exhibit enhanced survival

increased B cell proliferation ( J:166155 )

• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not

• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice

integument

abnormal coat appearance ( J:166155 )

• mutants exhibit ruffled fur by 4 months of age

mortality/aging

premature death ( J:166155 )

• severe morbidity and death occurs in all mutants by 1 year of age

neoplasm

increased lymphoma incidence ( J:166155 )

• mutants develop marginal zone lymphoma, and less frequently, follicular B cell lymphoma or centroblastic lymphoma

increased follicular lymphoma incidence ( J:166155 )

increased splenic marginal zone lymphoma incidence ( J:166155 )

• mutants develop spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma

increased malignant tumor incidence ( J:166155 )

• lymphoma infiltrates are seen in nonlymphoid tissues, including liver, lung, heart, and kidney

increased plasmacytoma incidence ( J:166155 )

cellular

increased B cell proliferation ( J:166155 )

• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not

• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
B-cell lymphoma		DOID:707		J:166155

Genotype
MGI:4829792

cn32

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19^tm1(cre)Cgn; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

immune system

immune system phenotype ( J:83213 )

N • the population of B1 and MZ B cells that are absent in single homozygous CD19 mutants is restored

N • mutants are capable of forming germinal centers when immunized with sheep red blood cells

Genotype
MGI:5543907

cn33

• Allelic Composition: Braf^tm1Mmcm/Braf^tm1Mmcm; Nkx3-1^{tm4(cre/ERT2)Mms}/Nkx3-1⁺; Pten^tm1Hwu/Pten⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

mortality/aging

premature death ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

neoplasm

increased prostate gland tumor incidence ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

♂ • tumors are large and highly proliferative and are primarily composed of luminal epithelial cells

♂ • tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration

♂ • tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative

♂ • treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation

increased prostate gland adenocarcinoma incidence ( J:191327 )

♂ • tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction

increased prostate intraepithelial neoplasia incidence ( J:191327 )

♂ • tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction

increased metastatic potential ( J:191327 )

♂ • metastases to lungs and lymph nodes are seen in tamoxifen treated mutants and disseminated tumor cells are seen in the bone marrow

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

♂ • tumors are large and highly proliferative and are primarily composed of luminal epithelial cells

♂ • tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration

♂ • tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative

♂ • treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation

increased prostate gland adenocarcinoma incidence ( J:191327 )

♂ • tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction

increased prostate intraepithelial neoplasia incidence ( J:191327 )

♂ • tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction

reproductive system

increased prostate gland tumor incidence ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

♂ • tumors are large and highly proliferative and are primarily composed of luminal epithelial cells

♂ • tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration

♂ • tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative

♂ • treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation

increased prostate gland adenocarcinoma incidence ( J:191327 )

♂ • tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction

increased prostate intraepithelial neoplasia incidence ( J:191327 )

♂ • tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:191327

Genotype
MGI:5704363

cn34

• Allelic Composition: Dicer1^tm1Tara/Dicer1^tm1Tara; Pten^tm1Hwu/Pten^tm1Hwu; Amhr2^tm3(cre)Bhr/Amhr2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd

neoplasm

increased metastatic potential ( J:182161 )

♀ • fallopian tube cancers subsequently spread to envelop the ovaries and then aggressively metastasize throughout the abdominal cavity, including the mesentery and pancreas, with prominent cancer lesions on the diaphragm and peritoneal membrane

increased carcinoma incidence ( J:182161 )

♀ • females develop early high-grade serous carcinomas in the fallopian tube

increased ovarian carcinoma incidence ( J:182161 )

♀ • tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer

♀ • origin of the serous carcinomas, however is the fallopian tube

mortality/aging

premature death ( J:182161 )

♀ • after developing ascites, 100% of females die from the metastatic cancers between 6.5 and 13 months of age

reproductive system

increased ovarian carcinoma incidence ( J:182161 )

♀ • tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer

♀ • origin of the serous carcinomas, however is the fallopian tube

abnormal oviduct morphology ( J:182161 )

♀ • abnormal proliferation begins in the stromal compartment, not in the epithelial layer, of the fallopian tube; tumor cells in the stroma express epithelial markers indicating that stromal cells in the fallopian tube undergo a transition to an epithelial cell type during carcinoma formation

homeostasis/metabolism

ascites ( J:182161 )

♀

endocrine/exocrine glands

increased ovarian carcinoma incidence ( J:182161 )

♀ • tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer

♀ • origin of the serous carcinomas, however is the fallopian tube

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:182161

Genotype
MGI:5704370

cn35

• Allelic Composition: Dicer1^tm1Tara/Dicer1^tm1Tara; Pten^tm1Hwu/Pten^tm1Hwu; Trp53^tm2Tyj/Trp53⁺; Amhr2^tm3(cre)Bhr/Amhr2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd

neoplasm

increased metastatic potential ( J:222579 )

♀ • mice show widespread peritoneal metastases, including omentum and diaphragm

♀ • the overall metastatic tumor burden in fallopian tube-removed mice is less extensive than that of intact mice

increased carcinoma incidence ( J:222579 )

♀ • mice develop massive high-grade serous carcinomas that always arise from the fallopian tube

♀ • however when fallopian tubes are removed, mice develop high-grade serous carcinomas originating from the ovary, indicating that the ovary can be a source of carcinomas but is less dominant in tumorigenesis than the fallopian tube

increased ovarian carcinoma incidence ( J:222579 )

♀ • ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer

mortality/aging

premature death ( J:222579 )

♀ • premature death starting around 6 months of age with all mice dying by around 8 months of age

♀ • fallopian tube-removed mice die at around 8-14 months of age after inducing ascites

homeostasis/metabolism

ascites ( J:222579 )

♀

endocrine/exocrine glands

increased ovarian carcinoma incidence ( J:222579 )

♀ • ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer

reproductive system

increased ovarian carcinoma incidence ( J:222579 )

♀ • ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:222579

Genotype
MGI:5704372

cn36

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Trp53^tm2Tyj/Trp53⁺; Amhr2^tm3(cre)Bhr/Amhr2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd

neoplasm

increased granulosa cell tumor incidence ( J:222579 )

♀ • 70% of mice develop granulosa-cell tumors in the ovary

increased ovarian carcinoma incidence ( J:222579 )

♀ • 30% of mice develop high-grade serous carcinoma originating in the ovary

♀ • however, mice do not develop serous carcinomas originating from the fallopian tube

increased metastatic potential ( J:222579 )

♀ • serous carcinoma spreads throughout the peritoneal cavity, to the omentum and across the peritoneal membrane, including the mesentery and diaphragm

mortality/aging

premature death ( J:222579 )

♀ • median survival is 11.2 months of age, with mice dying between 7.6 and 15.3 months of age

homeostasis/metabolism

ascites ( J:222579 )

♀

reproductive system

increased granulosa cell tumor incidence ( J:222579 )

♀ • 70% of mice develop granulosa-cell tumors in the ovary

increased ovarian carcinoma incidence ( J:222579 )

♀ • 30% of mice develop high-grade serous carcinoma originating in the ovary

♀ • however, mice do not develop serous carcinomas originating from the fallopian tube

endocrine/exocrine glands

increased granulosa cell tumor incidence ( J:222579 )

♀ • 70% of mice develop granulosa-cell tumors in the ovary

increased ovarian carcinoma incidence ( J:222579 )

♀ • 30% of mice develop high-grade serous carcinoma originating in the ovary

♀ • however, mice do not develop serous carcinomas originating from the fallopian tube

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:222579

Genotype
MGI:5007685

cn37

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(IghelMD4)4Ccg/0; Tg(ML5sHEL)5Ccg/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

immune system

abnormal peripheral B cell anergy ( J:155314 )

• failed tolerance induction resulting in abundant autoantibody production, indicating that B cells are prevented from acquiring an anergic state

• B cells have about 10 fold lower bound HEL than in mutants with intact Pten, suggesting that receptor occupancy is reduced on mutant autoreactive B cells and that less HEL is available in adults for inducing and sustaining anergy

• increasing the concentration of free self-antigen confers an anergic phenotype on mutant B cells, but they remain long-lived

Genotype
MGI:4944270

cn38

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA

hematopoietic system

enlarged thymus ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged thymus

enlarged spleen ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged spleen

neoplasm

increased acute lymphoblastic leukemia incidence ( J:169097 )

• mice injected with pIpC to induce Pten deletion, develop myeloproliferative disease and T-cell acute lymphoblastic leukemia, but at a slower rate than in single Pten mutants

mortality/aging

premature death ( J:169097 )

• mean survival time of mice injected with pIpC to induce Pten deletion is 46 days

immune system

enlarged thymus ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged thymus

enlarged spleen ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged spleen

endocrine/exocrine glands

enlarged thymus ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged thymus

growth/size/body

enlarged spleen ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged spleen

Genotype
MGI:4838529

cn39

• Allelic Composition: Akt2^tm1.1Mbb/Akt2^tm1.1Mbb; Pten^tm1Hwu/Pten^tm1Hwu; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA

homeostasis/metabolism

hyperglycemia ( J:160759 )

• about 25-30% increase in fasting glucose levels at 1 month of age

impaired glucose tolerance ( J:160759 )

• glucose intolerance

liver/biliary system

liver/biliary system phenotype ( J:160759 )

N • the liver phenotype observed in single Pten mutants is significantly reduced, with liver weights, triglyceride levels in the liver and fatty liver almost similar to controls

abnormal liver morphology ( J:218587 )

♂ • progenitor cell accumulation in the periductal region of livers occurs later than in single conditional Pten homozygotes, when injury conditions are already present

decreased susceptibility to hepatic steatosis ( J:218587 )

♂ • mice do not show development of steatosis compared to single conditional Pten homozygotes

neoplasm

increased tumor latency ( J:218587 )

♂ • mice exhibit a 6-month delay in liver tumor onset compared to conditional Pten homozygotes

♂ • no mice develop liver tumors between 9 and 12 months of age and 25% of mice older than 12 months develop liver nodules

♂ • however, treatment of 3 month old mice with 3,5-dietoxycarbonyl-1,4 dihydrocollidine (DDC) to induce liver injury leads to massive expansion of hepatic progenitors and development of premalignant lesions

Genotype
MGI:3844324

cn40

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB

mortality/aging

premature death ( J:146760 )

• all mice treated with an adenovirus expressing cre die by 6 months of age

neoplasm

increased carcinoma incidence ( J:146760 )

• urinary bladder tumors in Adeno-cre treated mice are of epithelial origins and exhibit features of carcinoma in situ and high-grade invasive carcinoma with areas of transitional cell, squamous, and sarcomatoid carcinoma

increased urinary bladder carcinoma incidence ( J:146760 )

• by 6 months, all mice treated with an adenovirus expressing cre (Adeno-cre) develop large urinary bladder tumors unlike wild-type mice

• by 4 to 6 months, 60% of Adeno-cre treated mice exhibit metastasis in the local lymph nodes, spleen, liver, and diaphragm

• however, treatment of mice with rapamycin following Adeno-cre injection prevents urinary bladder tumor formation

renal/urinary system

increased urinary bladder carcinoma incidence ( J:146760 )

• by 6 months, all mice treated with an adenovirus expressing cre (Adeno-cre) develop large urinary bladder tumors unlike wild-type mice

• by 4 to 6 months, 60% of Adeno-cre treated mice exhibit metastasis in the local lymph nodes, spleen, liver, and diaphragm

• however, treatment of mice with rapamycin following Adeno-cre injection prevents urinary bladder tumor formation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
urinary bladder cancer		DOID:11054	OMIM:109800	J:146760

Genotype
MGI:4840094

cn41

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Pten^tm1Hwu/Pten⁺; Trp53^tm1Tyj/Trp53⁺; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S4/SvJae * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:134611 )

• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity

behavior/neurological

increased startle reflex ( J:134611 )

• exaggerated startle response

ataxia ( J:134611 )

• ataxic gait

unidirectional circling ( J:134611 )

seizures ( J:134611 )

• generalized motor seizures

nervous system

seizures ( J:134611 )

• generalized motor seizures

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas

• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1^tm1Par and Trp53^tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes

neoplasm

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas

• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1^tm1Par and Trp53^tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant astrocytoma		DOID:3069		J:134611

Genotype
MGI:4836240

cn42

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(CAG-Bgeo/ALPP)1Lbe/0; Tg(Cela1-cre/ERT)1Dam/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:102226 )

N • 4 weeks after tamoxifen injections to induce Cre expression, pancreata exhibit no ductal metaplasia

Genotype
MGI:4836647

cn43

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

mortality/aging

premature death ( J:161841 )

digestive/alimentary system

megacolon ( J:161841 )

• mutants develop megacolon later in life

abnormal salivary gland morphology ( J:161841 )

• mutants develop hyperplasia of the salivary glands later in life

endocrine/exocrine glands

abnormal salivary gland morphology ( J:161841 )

• mutants develop hyperplasia of the salivary glands later in life

nervous system

increased brain size ( J:161841 )

abnormal brain white matter morphology ( J:161841 )

• increase in white matter volume

• progressive enlargement of all white matter tracts

abnormal corpus callosum morphology ( J:161841 )

• myelinated axons of the corpus callosum that intermingle with glial cells are in disarray

• density of myelinated axons in the ventral corpus callosum is decreased by 36.6% at 3 months of age

abnormal oligodendrocyte morphology ( J:161841 )

• oligodendroglial hypertrophy is seen at 4 months of age

abnormal Schwann cell morphology ( J:161841 )

• increase in numbers of myelinating and nonmyelinating Schwann cells

abnormal myelin sheath morphology ( J:161841 )

• increase in myelin sheath thickness

abnormal sciatic nerve morphology ( J:161841 )

• sciatic nerves are increased in size

• myelinated axons are more loosely spaced in sciatic nerves

• number of myelinated axons in the sciatic nerve is higher at 3 months of age; increase in myelination is primarily for small caliber axons

hypermyelination ( J:161841 )

• hypermyelination in both white and gray matter

• hypermyelination is primarily a consequence of additional membrane wraps and not by altered ultrastructure

• increase in myelin thickness is seen for axons of all calibers, however not all fibers are visibly hypermyelinated

• however, do not see ectopic myelination of CNS axons that normally are unmyelinated

• normally nonmyelinated C-fiber axons are spirally enwrapped by Remak Schwann cells; up to 10 membrane layers per axon are seen resulting in non compacted myelin

• Remak Schwann cells also ensheath bundles of collagen fibrils

• myelin outfoldings of variable length and aberrant myelin depositions are seen in the corpus callosum

vision/eye

cataract ( J:161841 )

• mutants develop cataracts later in life

reproductive system

reduced fertility ( J:161841 )

• poor breeding

Genotype
MGI:4944273

cn44

• Allelic Composition: Errfi1^tm1Jwj/Errfi1^tm1Jwj; Pgr^tm2(cre)Lyd/Pgr⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

mortality/aging

premature death ( J:162027 )

• survival time of double mutants is shorter than either single mutant, with mice dying by 16 weeks of age

reproductive system

increased endometrial carcinoma incidence ( J:162027 )

♀ • development of endometrial cancer is accelerated compared to either single mutant

abnormal endometrium morphology ( J:162027 )

♀ • decrease in the number of apoptotic cells in the endothelium epithelium compared to single Pten mutants

♀ • proliferation is increased in the endothelium epithelium

endometrium hyperplasia ( J:162027 )

♀ • mutants exhibit endometrial hyperplasia at 2 weeks of age and develop endometrial adenocarcinoma at 4 weeks of age

♀ • however, myometrial hyperplasia is not observed in the uteri of mutants

increased uterus weight ( J:162027 )

♀ • increase in uterine weight at 2 weeks of age, with weight at 4 weeks greater than in single Pten mutants

neoplasm

increased metastatic potential ( J:162027 )

• mutants exhibit distant metastases into the ovary, diaphragmatic skeletal muscle, lymph node, colon and pancreas

increased endometrial carcinoma incidence ( J:162027 )

♀ • development of endometrial cancer is accelerated compared to either single mutant

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endometrial cancer		DOID:1380	OMIM:608089	J:162027

Genotype
MGI:4839214

cn45

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Scgb1a1^{tm1.1(cre)Fjd}/Scgb1a1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

normal phenotype

no abnormal phenotype detected ( J:131721 )

• mice are viable and exhibit not visible abnormalities and remain healthy throughout 12 months of study, with normal lungs

Genotype
MGI:4944272

cn46

• Allelic Composition: Pgr^tm2(cre)Lyd/Pgr⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

mortality/aging

premature death ( J:218222 )

♀ • mice display a progressive decline in survival due to the development of endometrial cancer; all mice die by ~50 weeks of age

reproductive system

increased endometrial carcinoma incidence ( J:162027 , J:218222 )

♀ • mice develop endometrial adenocarcinoma with invasion into the myometrium at 2 months of age (J:162027)

♀ • mice develop endometrial adenocarcinoma at 2 and 3 months of ages as characterized by neoplastic endometrial glands invading through the myometrium (J:218222)

♀ • treatment with U0126, an effective inhibitor of MAPK/ERK kinase, suppresses endometrial cancer progression, as shown by the arrest of tumors at the hyperplastic or normal stage (J:218222)

endometrium hyperplasia ( J:162027 )

♀ • mice exhibit endometrial hyperplasia at 4 weeks of age

decreased uterus weight ( J:218222 )

♀ • mice treated with U0126, an effective inhibitor of MAPK/ERK kinase, display a significant decrease in uterine weight relative to mice treated with vehicle

increased uterus weight ( J:162027 , J:218222 )

♀ • increase in uterine weight at 2 weeks of age (J:162027)

♀ • at 3 months of age, mice show a significant increase in uterine/body weight ratio relative to controls (J:218222)

abnormal uterus physiology ( J:162027 )

♀ • proliferation is increased in the endothelium epithelium

neoplasm

increased endometrial carcinoma incidence ( J:162027 , J:218222 )

♀ • mice develop endometrial adenocarcinoma with invasion into the myometrium at 2 months of age (J:162027)

♀ • mice develop endometrial adenocarcinoma at 2 and 3 months of ages as characterized by neoplastic endometrial glands invading through the myometrium (J:218222)

♀ • treatment with U0126, an effective inhibitor of MAPK/ERK kinase, suppresses endometrial cancer progression, as shown by the arrest of tumors at the hyperplastic or normal stage (J:218222)

increased papilloma incidence ( J:218222 )

♀ • mice develop vaginal papillomas

Genotype
MGI:4839216

cn47

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten^tm1Hwu; Scgb1a1^{tm1.1(cre)Fjd}/Scgb1a1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

mortality/aging

premature death ( J:131721 )

• mean survival is 8 weeks

immune system

lung inflammation ( J:131721 )

• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression

respiratory system

lung inflammation ( J:131721 )

• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression

increased lung tumor incidence ( J:131721 )

• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants

• mutants develop distinct bronchial and alveolar tumors

increased lung adenoma incidence ( J:131721 )

• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions

increased lung carcinoma incidence ( J:131721 )

• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation

increased lung adenocarcinoma incidence ( J:131721 )

• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma

tachypnea ( J:131721 )

• by 2 months of age, mutants exhibit tachypnea

neoplasm

increased lung tumor incidence ( J:131721 )

• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants

• mutants develop distinct bronchial and alveolar tumors

increased lung adenoma incidence ( J:131721 )

• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions

increased lung carcinoma incidence ( J:131721 )

• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation

increased lung adenocarcinoma incidence ( J:131721 )

• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma

growth/size/body

weight loss ( J:131721 )

• by 2 months of age, mutants exhibit weight loss

Genotype
MGI:4839562

cn48

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Cdh5-cre)7Mlia/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6 * FVB/N

mortality/aging

premature death ( J:135172 )

• die before P68 with vascular complications

hematopoietic system

abnormal definitive hematopoiesis ( J:135172 )

• 100% of mutants develop myeloproliferative disorder at about P30

cardiovascular system

abnormal blood vessel morphology ( J:135172 )

• mutants exhibit vascular complication

Genotype
MGI:4839561

cn49

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1^tm2Kem; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Cdh5-cre)7Mlia/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6 * FVB/N

mortality/aging

embryonic lethality, complete penetrance ( J:135172 )

• embryonic lethal

Genotype
MGI:4849443

cn50

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Pten^tm1Hwu/Pten⁺; Tg(Gfap-cre)77.6Mvs/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6NHsd

neoplasm

neoplasm ( J:154673 )

N • mutants do not develop tumors

Genotype
MGI:3813633

cn51

• Allelic Composition: Pgr^tm2(cre)Lyd/Pgr⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:139053 )

• impaired survival is seen beginning around 5 months of age

reproductive system

increased endometrial carcinoma incidence ( J:139053 )

♀ • hyperplasia progresses to carcinoma by 1 month of age with invasion into the myometrium detected by 3 months of age

endometrium hyperplasia ( J:139053 )

♀ • by P10, luminal and glandular epithelial hyperplasia are seen

neoplasm

increased endometrial carcinoma incidence ( J:139053 )

♀ • hyperplasia progresses to carcinoma by 1 month of age with invasion into the myometrium detected by 3 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endometrial cancer		DOID:1380	OMIM:608089	J:139053

Genotype
MGI:5780554

cn52

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-Errfi1)Jwj}/?; Pgr^tm2(cre)Lyd/Pgr⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:218222 )

♀ • mice exhibit significantly increased survival time relative to mice that are homozygous for Pten^tm1Hwu and heterozygous for Pgr^tm2(cre)Lyd, with >50% of mice still viable at 64 weeks of age

♀ • mice do not die due to the development of endometrial cancer

reproductive system

endometrium hyperplasia ( J:218222 )

♀ • mice exhibit endometrial hyperplasia at 2 months but not at 3 months of age

♀ • however, endometrial adenocarcinoma with invasion into the myometrium is not observed due to inhibition of ERK1/2 phosphorylation

increased uterus weight ( J:218222 )

♀ • at 3 months of age, mice show a significantly reduced increase in uterine/body weight ratio relative to mice that are homozygous for Pten^tm1Hwu and heterozygous for Pgr^tm2(cre)Lyd

abnormal uterus physiology ( J:218222 )

♀ • at 2 months of age, mice show a significantly reduced uterine epithelial cell proliferation relative to mice that are homozygous for Pten^tm1Hwu and heterozygous for Pgr^tm2(cre)Lyd

neoplasm

increased papilloma incidence ( J:218222 )

♀ • mice develop vaginal papillomas

Genotype
MGI:5009703

cn53

• Allelic Composition: Ar^tm1Verh/Y; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2

neoplasm

increased prostate gland adenocarcinoma incidence ( J:172730 )

♂ • mutants develop adenocarcinoma in the dorsolateral lobes of the prostate

♂ • cancer progression is similar to single conditional Pten mice

♂ • proliferation and apoptotic indexes are increased in the cancers, most notably in the proximal regions of the dorsal-lateral lobe

♂ • mutant tumors contain low or no p63+ cells, similar to human prostate cancer

♂ • castrated mutants develop cancer outgrowths in the dorsolateral lobes, indicating that mutants develop castrate-resistant prostate cancer

♂ • castrated mice treated with rapamycin show a reduction in prostate volume and reduced prostate proliferation

reproductive system

increased prostate gland adenocarcinoma incidence ( J:172730 )

♂ • mutants develop adenocarcinoma in the dorsolateral lobes of the prostate

♂ • cancer progression is similar to single conditional Pten mice

♂ • proliferation and apoptotic indexes are increased in the cancers, most notably in the proximal regions of the dorsal-lateral lobe

♂ • mutant tumors contain low or no p63+ cells, similar to human prostate cancer

♂ • castrated mutants develop cancer outgrowths in the dorsolateral lobes, indicating that mutants develop castrate-resistant prostate cancer

♂ • castrated mice treated with rapamycin show a reduction in prostate volume and reduced prostate proliferation

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:172730 )

♂ • mutants develop adenocarcinoma in the dorsolateral lobes of the prostate

♂ • cancer progression is similar to single conditional Pten mice

♂ • proliferation and apoptotic indexes are increased in the cancers, most notably in the proximal regions of the dorsal-lateral lobe

♂ • mutant tumors contain low or no p63+ cells, similar to human prostate cancer

♂ • castrated mutants develop cancer outgrowths in the dorsolateral lobes, indicating that mutants develop castrate-resistant prostate cancer

♂ • castrated mice treated with rapamycin show a reduction in prostate volume and reduced prostate proliferation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:172730

Genotype
MGI:4840096

cn54

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Pten^tm1Hwu/Pten⁺; Trp53^tm1Elee/Trp53⁺; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:134611 )

• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity

behavior/neurological

increased startle reflex ( J:134611 )

• exaggerated startle response

ataxia ( J:134611 )

• ataxic gait

unidirectional circling ( J:134611 )

seizures ( J:134611 )

• generalized motor seizures

nervous system

seizures ( J:134611 )

• generalized motor seizures

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• mutants develop astrocytomas

• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci

neoplasm

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• mutants develop astrocytomas

• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci

Genotype
MGI:4839510

cn55

• Allelic Composition: Erbb2^{tm8(Erbb2)Mul}/Erbb2⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(MMTV-cre)7Mul/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N

neoplasm

increased mammary gland tumor incidence ( J:133305 )

• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 2.4 compared with 15.5 months

• 25% of tumors are adenomyoepitheliomas

• 25% of tumors are Erbb2 type neoplasms

• 25% of tumors exhibit squamous metaplasia and retention of myoepithelium

• 25% of tumors are glandular, composed of distinctive large cell population that are a signature phenotype of mammary tumors in these mice

• tumors are similar to HER2 and basal-like subtype of human breast cancer

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:133305 )

• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 2.4 compared with 15.5 months

• 25% of tumors are adenomyoepitheliomas

• 25% of tumors are Erbb2 type neoplasms

• 25% of tumors exhibit squamous metaplasia and retention of myoepithelium

• 25% of tumors are glandular, composed of distinctive large cell population that are a signature phenotype of mammary tumors in these mice

• tumors are similar to HER2 and basal-like subtype of human breast cancer

integument

increased mammary gland tumor incidence ( J:133305 )

• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 2.4 compared with 15.5 months

• 25% of tumors are adenomyoepitheliomas

• 25% of tumors are Erbb2 type neoplasms

• 25% of tumors exhibit squamous metaplasia and retention of myoepithelium

• 25% of tumors are glandular, composed of distinctive large cell population that are a signature phenotype of mammary tumors in these mice

• tumors are similar to HER2 and basal-like subtype of human breast cancer

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:133305

Genotype
MGI:4839508

cn56

• Allelic Composition: Erbb2^{tm8(Erbb2)Mul}/Erbb2⁺; Pten^tm1Hwu/Pten⁺; Tg(MMTV-cre)7Mul/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N

neoplasm

increased mammary gland tumor incidence ( J:133305 )

• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months

• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors

• tumors are similar to basal-like subtype of human breast cancer

increased metastatic potential ( J:133305 )

• 35% incidence of lung metastases compared with 5% in single Erbb2 mutants

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:133305 )

• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months

• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors

• tumors are similar to basal-like subtype of human breast cancer

integument

increased mammary gland tumor incidence ( J:133305 )

• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months

• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors

• tumors are similar to basal-like subtype of human breast cancer

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:133305

Genotype
MGI:3783573

cn57

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11⁺; Pten^tm1Hwu/Pten⁺; Tg(CD2-icre)4Kio/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/10 * CBA/Ca

immune system

increased germinal center B cell number ( J:133215 )

• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

abnormal T cell number ( J:133215 )

• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

hematopoietic system

increased germinal center B cell number ( J:133215 )

• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

abnormal T cell number ( J:133215 )

• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

Genotype
MGI:6384016

cn58

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Ptpn11^tm1Gsf/Ptpn11^tm1Gsf; Tg(Six3-cre)69Frty/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

vision/eye

retina ganglion cell degeneration ( J:174095 )

• much thinner at age P21

optic nerve atrophy ( J:174095 )

• much thinner at age P21

thin retina ganglion layer ( J:174095 )

• severe reduction at age P21

thin retina inner nuclear layer ( J:174095 )

• severe reduction at age P21

thin retina outer nuclear layer ( J:174095 )

• severe reduction at age P21

retina outer nuclear layer degeneration ( J:174095 )

• much thinner at age P21

retina degeneration ( J:174095 )

• much thinner at age P21

nervous system

retina ganglion cell degeneration ( J:174095 )

• much thinner at age P21

optic nerve atrophy ( J:174095 )

• much thinner at age P21

Genotype
MGI:4836239

cn59

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pdx1-cre)89.1Dam/0; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6 * CBA

neoplasm

increased pancreatic acinar cell carcinoma incidence ( J:102226 )

• 1 of 5 mutants develop a small acinar carcinoma

increased pancreatic ductal adenocarcinoma incidence ( J:102226 )

• 2 of 5 mutants develop papillary adenocarcionomas at 4 and 6 months of age

endocrine/exocrine glands

increased pancreatic acinar cell carcinoma incidence ( J:102226 )

• 1 of 5 mutants develop a small acinar carcinoma

increased pancreatic ductal adenocarcinoma incidence ( J:102226 )

• 2 of 5 mutants develop papillary adenocarcionomas at 4 and 6 months of age

Genotype
MGI:4844100

cn60

• Allelic Composition: Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Fabp1-cre)1Jig/0
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * FVB/N

renal/urinary system

increased urinary bladder carcinoma incidence ( J:106662 )

abnormal urinary bladder urothelium morphology ( J:106662 )

• bladder urothelium exhibits increased cell proliferation

neoplasm

increased urinary bladder carcinoma incidence ( J:106662 )

Genotype
MGI:4830361

cn61

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Fabp4-cre)1Abel/0
• Genetic Background: involves: 129S4/SvJae

adipose tissue

adipose tissue phenotype ( J:97588 )

N • no differences in body weight and fat storage

homeostasis/metabolism

decreased circulating insulin level ( J:97588 )

• fasting mutants exhibit a 2.1-fold decrease in plasma insulin levels compared to controls indicating enhanced insulin sensitivity

improved glucose tolerance ( J:97588 )

• during a glucose tolerance test, mutants show a blunted elevation of blood glucose; the mean peak increase in blood glucose is 19% lower than that of controls

• mutants are protected from developing streptozotocin-induced diabetes; they maintain normal glycemia and remain resistant to the development of hyperglycemia

increased insulin sensitivity ( J:97588 )

• mutants are more sensitive to insulin challenge (in insulin tolerance test), showing a 24% lower blood glucose at 60 min compared to wild-type mice

• insulin resistance is 1.9-fold lower for mutants than controls

abnormal cytokine level ( J:97588 )

• 36% lower serum concentrations of the adipocytokine resistin

immune system

abnormal cytokine level ( J:97588 )

• 36% lower serum concentrations of the adipocytokine resistin

Genotype
MGI:5688693

cn62

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(MMTV-cre)#Tfln/0
• Genetic Background: involves: 129S4/SvJae

reproductive system

abnormal mammary gland growth during pregnancy ( J:78415 )

♀ • mammary glands exhibit much larger lobules on the 13th day of pregnancy

neoplasm

increased mammary gland tumor incidence ( J:78415 )

• develop mammary gland tumors as early as 2 months of age

• tumor incidence is increased with shortened latencies in multiparous females

increased fibroadenoma incidence ( J:78415 )

• benign fibroadenomas

increased mammary adenocarcinoma incidence ( J:78415 )

• pleiomorphic adenocarcinomas

endocrine/exocrine glands

abnormal involution of the mammary gland ( J:78415 )

♀ • delay in the normal involution process and a decrease in cell apoptosis

abnormal mammary gland growth during pregnancy ( J:78415 )

♀ • mammary glands exhibit much larger lobules on the 13th day of pregnancy

abnormal mammary gland epithelium morphology ( J:78415 )

♀ • virgin mammary duct epithelium exhibits increased proliferation at 5 weeks and 14 weeks of age

abnormal branching of the mammary ductal tree ( J:78415 )

♀ • virgin mammary ducts develop excessive side branches or small protrusions at 6 weeks of age

mammary gland duct hyperplasia ( J:78415 )

♀ • mammary ducts grow much faster during puberty than in controls, leading to earlier occupancy of the fat pad and earlier disappearance of the terminal end buds than in controls

abnormal mammary gland lobule morphology ( J:78415 )

♀ • virgin glands contain many lobuloalveolar buds which are normally seen during pregnancy indicating an acceleration in lobuloalveolar-like precocious differentiation

increased mammary gland tumor incidence ( J:78415 )

• develop mammary gland tumors as early as 2 months of age

• tumor incidence is increased with shortened latencies in multiparous females

increased fibroadenoma incidence ( J:78415 )

• benign fibroadenomas

increased mammary adenocarcinoma incidence ( J:78415 )

• pleiomorphic adenocarcinomas

mammary gland hyperplasia ( J:78415 )

♀ • mammary glands after one pregnancy show intra-luminal focal cellular hyperplasia and dysplasia

integument

abnormal involution of the mammary gland ( J:78415 )

♀ • delay in the normal involution process and a decrease in cell apoptosis

abnormal mammary gland growth during pregnancy ( J:78415 )

♀ • mammary glands exhibit much larger lobules on the 13th day of pregnancy

abnormal mammary gland epithelium morphology ( J:78415 )

♀ • virgin mammary duct epithelium exhibits increased proliferation at 5 weeks and 14 weeks of age

abnormal branching of the mammary ductal tree ( J:78415 )

♀ • virgin mammary ducts develop excessive side branches or small protrusions at 6 weeks of age

mammary gland duct hyperplasia ( J:78415 )

♀ • mammary ducts grow much faster during puberty than in controls, leading to earlier occupancy of the fat pad and earlier disappearance of the terminal end buds than in controls

abnormal mammary gland lobule morphology ( J:78415 )

♀ • virgin glands contain many lobuloalveolar buds which are normally seen during pregnancy indicating an acceleration in lobuloalveolar-like precocious differentiation

increased mammary gland tumor incidence ( J:78415 )

• develop mammary gland tumors as early as 2 months of age

• tumor incidence is increased with shortened latencies in multiparous females

increased fibroadenoma incidence ( J:78415 )

• benign fibroadenomas

increased mammary adenocarcinoma incidence ( J:78415 )

• pleiomorphic adenocarcinomas

mammary gland hyperplasia ( J:78415 )

♀ • mammary glands after one pregnancy show intra-luminal focal cellular hyperplasia and dysplasia

Genotype
MGI:5014516

cn63

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S4/SvJae

neoplasm

increased ovary tumor incidence ( J:161953 )

♀ • mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination develop ovarian cancer eight weeks after injection

reproductive system

increased ovary tumor incidence ( J:161953 )

♀ • mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination develop ovarian cancer eight weeks after injection

endocrine/exocrine glands

increased ovary tumor incidence ( J:161953 )

♀ • mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination develop ovarian cancer eight weeks after injection

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:161953

Genotype
MGI:5014515

cn64

• Allelic Composition: Fas^tm1Ach/Fas^tm1Ach; Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S4/SvJae

neoplasm

decreased ovarian tumor incidence ( J:161953 )

• triple mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination are protected from developing ovarian cancer, with only 1 of 11 mice developing cancer compared to 9 of 12 double Kras and Pten mutants

endocrine/exocrine glands

decreased ovarian tumor incidence ( J:161953 )

• triple mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination are protected from developing ovarian cancer, with only 1 of 11 mice developing cancer compared to 9 of 12 double Kras and Pten mutants

reproductive system

decreased ovarian tumor incidence ( J:161953 )

• triple mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination are protected from developing ovarian cancer, with only 1 of 11 mice developing cancer compared to 9 of 12 double Kras and Pten mutants

Genotype
MGI:7543156

cn65

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pgc-cre,-secNluc)#Hcz/0
• Genetic Background: involves: 129S4/SvJae

neoplasm

increased mammary adenocarcinoma incidence ( J:338079 )

♀ • in mice with two or more pregnancies

♀ • however, virgin conditional mice do not develop breast cancer even after exposure to estrogen or progesterone and mice that do not breastfeed after more than 2 births fail to develop breast cancer

integument

increased mammary adenocarcinoma incidence ( J:338079 )

♀ • in mice with two or more pregnancies

♀ • however, virgin conditional mice do not develop breast cancer even after exposure to estrogen or progesterone and mice that do not breastfeed after more than 2 births fail to develop breast cancer

endocrine/exocrine glands

increased mammary adenocarcinoma incidence ( J:338079 )

♀ • in mice with two or more pregnancies

♀ • however, virgin conditional mice do not develop breast cancer even after exposure to estrogen or progesterone and mice that do not breastfeed after more than 2 births fail to develop breast cancer

Genotype
MGI:4430559

cn66

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Cr2-cre)3Cgn/0
• Genetic Background: involves: 129S4/SvJae

mortality/aging

preweaning lethality, complete penetrance ( J:157297 )

• no time point given

Genotype
MGI:4847591

cn67

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(CYP19A1-cre)1Jri/0
• Genetic Background: involves: 129S4/SvJae

endocrine/exocrine glands

decreased granulosa cell apoptosis ( J:138315 )

♀ • numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries

impaired luteal cell differentiation ( J:138315 )

♀ • the increased numbers of corpora lutea are at different stages of differentiation than in controls

♀ • steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active

increased granulosa cell proliferation ( J:138315 )

♀ • granulosa cells exhibit increased proliferation

increased corpora lutea number ( J:138315 )

♀ • after 3 months of age, ovaries contain increased numbers of corpora lutea

abnormal ovarian follicle morphology ( J:138315 )

♀ • females exhibit increased follicle growth

♀ • numbers of apoptotic follicles decreased in eCG-primed mutant ovaries

enlarged ovary ( J:138315 )

♀ • after 3 months of age, ovaries are larger and contain increased numbers of corpora lutea

growth/size/body

enlarged ovary ( J:138315 )

♀ • after 3 months of age, ovaries are larger and contain increased numbers of corpora lutea

reproductive system

decreased granulosa cell apoptosis ( J:138315 )

♀ • numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries

impaired luteal cell differentiation ( J:138315 )

♀ • the increased numbers of corpora lutea are at different stages of differentiation than in controls

♀ • steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active

increased granulosa cell proliferation ( J:138315 )

♀ • granulosa cells exhibit increased proliferation

increased corpora lutea number ( J:138315 )

♀ • after 3 months of age, ovaries contain increased numbers of corpora lutea

abnormal ovarian follicle morphology ( J:138315 )

♀ • females exhibit increased follicle growth

♀ • numbers of apoptotic follicles decreased in eCG-primed mutant ovaries

enlarged ovary ( J:138315 )

♀ • after 3 months of age, ovaries are larger and contain increased numbers of corpora lutea

increased superovulation rate ( J:138315 )

♀ • immature females primed with a superovulatory regiment of equine chorionic gonadotropin (eCG), followed by human CG, ovulate more oocytes than control mice, indicating advanced ovulation rate and increased ovulation

abnormal luteolysis ( J:138315 )

♀ • luteolysis is dramatically impaired and delayed in mutants on a superovulatory regimen of eCG/hCG compared to wild-type mice

enhanced female fertility ( J:138315 )

♀ • females give birth to approximately 20% more pups than controls during a 6-month breeding period

neoplasm

neoplasm ( J:138315 )

♀N • females do not develop ovarian tumors

cellular

decreased granulosa cell apoptosis ( J:138315 )

♀ • numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries

impaired luteal cell differentiation ( J:138315 )

♀ • the increased numbers of corpora lutea are at different stages of differentiation than in controls

♀ • steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active

increased granulosa cell proliferation ( J:138315 )

♀ • granulosa cells exhibit increased proliferation

Genotype
MGI:5816455

cn68

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Notch1)Dam}/Gt(ROSA)26Sor⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Adipoq-cre)1Evdr/0
• Genetic Background: involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6J * FVB/NJ

adipose tissue

abnormal brown adipose tissue morphology ( J:237232 )

• brown adipose tissue shows hypertrophy, accompanied by presence of large unilocular adipocytes

lipodystrophy ( J:237232 )

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:237232 )

N • mice shown normal glucose metabolism, with reversal of hyperglycemia to a level that is lower than in wild-type mice and normalized response to glucose challenge

neoplasm

increased liposarcoma incidence ( J:237232 )

• mice develop malignant sarcomas by 3 months of age at various locations of the body, including diaphragm, limb, spine, retroperitoneum, subcutaneous regions, and in the thoracic cavity

• multiple tumors of various sizes are seen in all mice

• tumors show classical biphasic neoplasm with one component of atypical lipomatous tumors and a second component of high-grade sarcoma indicating dedifferentiated liposarcoma

• tumors show heavy infiltration of inflammatory cells which are Cd45+/Ki67-

• treatment with rosigliatazone starting from 3 weeks of age prevents liposarcoma formation at 5 months of age

Genotype
MGI:5784501

cn69

• Allelic Composition: Foxo1^tm1Rdp/Foxo1^tm1.1Rdp; Foxo3^tm1Rdp/Foxo3^tm1.1Rdp; Pten^tm1Hwu/Pten^tm1Hwu; Tg(CYP19A1-cre)1Jri/0
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac

endocrine/exocrine glands

increased granulosa cell tumor incidence ( J:232961 )

♀ • 60% incidence of granulosa cell tumor occurrence, with early tumor development

♀ • granulosa cell tumors are either solid and surrounded by a thin layer of ovarian tissue containing a few growing follicles or are larger and contain tubular-like structures of different sizes and shapes surrounded by a basal lamina of collagen IV

♀ • mice injected with superovulatory levels of equine gonadotropin and human gonadotropin at 6 weeks of age develop large granulosa cell tumors early

homeostasis/metabolism

abnormal circulating hormone level ( J:232961 )

♀ • tumor bearing mice exhibit increased levels of serum inhibin A and inhibin B

suppressed circulating follicle stimulating hormone level ( J:232961 )

♀ • serum follicle stimulating hormone levels are below the level of detection in tumor bearing mice

decreased circulating luteinizing hormone level ( J:232961 )

♀ • serum luteinizing hormone levels are below the level of detection in tumor bearing mice

neoplasm

increased granulosa cell tumor incidence ( J:232961 )

♀ • 60% incidence of granulosa cell tumor occurrence, with early tumor development

♀ • granulosa cell tumors are either solid and surrounded by a thin layer of ovarian tissue containing a few growing follicles or are larger and contain tubular-like structures of different sizes and shapes surrounded by a basal lamina of collagen IV

♀ • mice injected with superovulatory levels of equine gonadotropin and human gonadotropin at 6 weeks of age develop large granulosa cell tumors early

reproductive system

increased granulosa cell tumor incidence ( J:232961 )

♀ • 60% incidence of granulosa cell tumor occurrence, with early tumor development

♀ • granulosa cell tumors are either solid and surrounded by a thin layer of ovarian tissue containing a few growing follicles or are larger and contain tubular-like structures of different sizes and shapes surrounded by a basal lamina of collagen IV

♀ • mice injected with superovulatory levels of equine gonadotropin and human gonadotropin at 6 weeks of age develop large granulosa cell tumors early

Genotype
MGI:4848147

cn70

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Rictor^tm1.1Mgn/Rictor^tm1.1Mgn
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac

endocrine/exocrine glands

abnormal prostate gland duct morphology ( J:144810 )

♂ • prostatic ductules of mutants infected with an adenovirus expressing Cre recombinase exhibit a mixed phenotype containing mostly normal, organized epithelial cells and patches of large, disorganized hyperplastic cells; inefficient deletion of Rictor is seen in the patches of disorganized hyperplastic cells

abnormal prostate gland epithelium morphology ( J:144810 )

♂ • prostate tissue histology of mutants infected with an adenovirus expressing Cre recombinase appears normal except that epithelial cells are slightly smaller

reproductive system

abnormal prostate gland duct morphology ( J:144810 )

♂ • prostatic ductules of mutants infected with an adenovirus expressing Cre recombinase exhibit a mixed phenotype containing mostly normal, organized epithelial cells and patches of large, disorganized hyperplastic cells; inefficient deletion of Rictor is seen in the patches of disorganized hyperplastic cells

abnormal prostate gland epithelium morphology ( J:144810 )

♂ • prostate tissue histology of mutants infected with an adenovirus expressing Cre recombinase appears normal except that epithelial cells are slightly smaller

neoplasm

decreased tumor incidence ( J:144810 )

• mutants infected with an adenovirus expressing Cre recombinase do not develop prostate adenocarcinoma

Genotype
MGI:5008147

cn71

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Rictor^tm1.1Mgn/Rictor^tm1.1Mgn; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * BALB/c * C57BL/6 * DBA

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:170129 )

• average beta cell size is increased by 31% compared to controls and by 15% compared to single conditional Pten mutants

• however, mutants show normal beta cell proliferation

decreased pancreatic beta cell mass ( J:170129 )

• beta cell mass is about 40% lower than that of single conditional Pten mutants

growth/size/body

postnatal growth retardation ( J:170129 )

homeostasis/metabolism

abnormal glucose homeostasis ( J:170129 )

• total glucose excursion is lower compared to single conditional Rictor mutants

hypoglycemia ( J:170129 )

• fed blood glucose concentration remains similar to the controls, however mutants show a lower blood glucose concentration at 30 and 60 min after an intraperitoneal glucose bolus compared to single conditional Rictor mutants

decreased circulating insulin level ( J:170129 )

• mutants exhibit lower plasma insulin levels 15 min after glucose challenge and lower total insulin output compared with controls

• however, insulin secretion by glucose stimulated islets is similar to controls and pancreatic insulin content is unchanged

Genotype
MGI:4365721

cn72

• Allelic Composition: Nkx3-1^{tm4(cre/ERT2)Mms}/Nkx3-1⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6

neoplasm

increased prostate gland adenocarcinoma incidence ( J:153425 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion

increased prostate intraepithelial neoplasia incidence ( J:153425 , J:191327 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion (J:153425)

♂ • mutants show extensive prostate intraepithelial neoplasia (PIN) III and PIN IV 9-12 months after tamoxifen induction, with some areas of squamous papilloma, however mutants rarely develop lethal prostate cancer up to 2 years following tamoxifen induction (J:191327)

reproductive system

increased prostate gland adenocarcinoma incidence ( J:153425 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion

increased prostate intraepithelial neoplasia incidence ( J:153425 , J:191327 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion (J:153425)

♂ • mutants show extensive prostate intraepithelial neoplasia (PIN) III and PIN IV 9-12 months after tamoxifen induction, with some areas of squamous papilloma, however mutants rarely develop lethal prostate cancer up to 2 years following tamoxifen induction (J:191327)

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:153425 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion

increased prostate intraepithelial neoplasia incidence ( J:153425 , J:191327 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion (J:153425)

♂ • mutants show extensive prostate intraepithelial neoplasia (PIN) III and PIN IV 9-12 months after tamoxifen induction, with some areas of squamous papilloma, however mutants rarely develop lethal prostate cancer up to 2 years following tamoxifen induction (J:191327)

Genotype
MGI:6198768

cn73

• Allelic Composition: Eif2ak3^tm1.2Drc/Eif2ak3^tm1.2Drc; Pten^tm1Hwu/Pten^tm1Hwu; Tg(CAG-MYC,-GFP*)#Rugg/0; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA/2

endocrine/exocrine glands

decreased prostate gland tumor incidence ( J:261540 )

♂ • mice show reduced prostate growth, with a decrease prostate cancer progression and cell proliferation compared to Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/0 Tg(CAG-MYC,-GFP)#Rugg/0 mice

neoplasm

decreased prostate gland tumor incidence ( J:261540 )

♂ • mice show reduced prostate growth, with a decrease prostate cancer progression and cell proliferation compared to Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/0 Tg(CAG-MYC,-GFP)#Rugg/0 mice

reproductive system

decreased prostate gland tumor incidence ( J:261540 )

♂ • mice show reduced prostate growth, with a decrease prostate cancer progression and cell proliferation compared to Pten^tm1Hwu/Pten^tm1Hwu Tg(Pbsn-cre)4Prb/0 Tg(CAG-MYC,-GFP)#Rugg/0 mice

Genotype
MGI:4839217

cn74

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Smad4^tm2.1Cxd/Smad4^tm2.1Cxd; Tg(Alb1-cre)1Dlr/0
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * FVB/N

mortality/aging

premature death ( J:111718 )

• all mutants die before 10 months of age

endocrine/exocrine glands

abnormal bile duct morphology ( J:111718 )

• increase in branching of bile ducts in the liver

increased cholangiocarcinoma incidence ( J:111718 )

• at 2 months of age, hyperplastic foci emerge from bile ducts and continue to grow, leading to tumor formation in all mice at 4-7 months of age; tumors are intrahepatic cholangiocellular carcinoma

liver/biliary system

abnormal bile duct morphology ( J:111718 )

• increase in branching of bile ducts in the liver

increased cholangiocarcinoma incidence ( J:111718 )

• at 2 months of age, hyperplastic foci emerge from bile ducts and continue to grow, leading to tumor formation in all mice at 4-7 months of age; tumors are intrahepatic cholangiocellular carcinoma

enlarged liver ( J:111718 )

• increase in liver size and weight due to fat accumulation in the liver

increased liver weight ( J:111718 )

hepatic steatosis ( J:111718 )

neoplasm

increased cholangiocarcinoma incidence ( J:111718 )

• at 2 months of age, hyperplastic foci emerge from bile ducts and continue to grow, leading to tumor formation in all mice at 4-7 months of age; tumors are intrahepatic cholangiocellular carcinoma

growth/size/body

enlarged liver ( J:111718 )

• increase in liver size and weight due to fat accumulation in the liver

increased liver weight ( J:111718 )

Genotype
MGI:4942351

cn75

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Amhr2^tm3(cre)Bhr/Amhr2⁺
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd

reproductive system

reproductive system phenotype ( J:142150 )

N • most females lack ovarian abnormalities

increased granulosa cell tumor incidence ( J:142150 , J:222579 )

♀ • 5 of 70 females developed ovarian tumors (J:142150)

♀ • ovarian tumors are granulosa cell tumors (J:142150)

♀ • 65% of mice develop granulosa-cell type tumors in the ovary (J:222579)

♀ • however, mice do not develop ovarian or fallopian tube high grade serous carcinoma (J:222579)

abnormal pregnancy ( J:142150 )

♀ • many females fail to carry pregnancies to term

decreased litter size ( J:142150 )

• many females have small litters due to fetal death after E9.5

neoplasm

increased granulosa cell tumor incidence ( J:142150 , J:222579 )

♀ • 5 of 70 females developed ovarian tumors (J:142150)

♀ • ovarian tumors are granulosa cell tumors (J:142150)

♀ • 65% of mice develop granulosa-cell type tumors in the ovary (J:222579)

♀ • however, mice do not develop ovarian or fallopian tube high grade serous carcinoma (J:222579)

increased metastatic potential ( J:142150 )

• ganulosa cell tumors are aggressive and metastasize to the lungs

endocrine/exocrine glands

increased granulosa cell tumor incidence ( J:142150 , J:222579 )

♀ • 5 of 70 females developed ovarian tumors (J:142150)

♀ • ovarian tumors are granulosa cell tumors (J:142150)

♀ • 65% of mice develop granulosa-cell type tumors in the ovary (J:222579)

♀ • however, mice do not develop ovarian or fallopian tube high grade serous carcinoma (J:222579)

Genotype
MGI:4941746

cn76

• Allelic Composition: Amhr2^tm3(cre)Bhr/Amhr2⁺; Ctnnb1^tm1Mmt/Ctnnb1⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * 129X1/SvJ

neoplasm

increased ovary tumor incidence ( J:142150 )

♀ • presence of nests of dysplastic cells are seen in the ovaries of newborn mice and E20.5, but not E18.5, indicating that tumor growth begins perinatally

increased granulosa cell tumor incidence ( J:149060 )

• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age

increased testis tumor incidence ( J:149060 )

♂ • 100% penetrance of aggressive testicular cancer

♂ • tumors are first observable at 5 weeks of age, and by 3 months of age, about 70% of mice have unilateral testicular tumors and 30% have bilateral tumors

♂ • tumors exhibit characteristics of granulosa cell tumors of the testis and not Sertoli cell tumors

increased metastatic potential ( J:142150 , J:149060 )

• metastasis is not observed, but this might be that mice do not have sufficient time to develop metastasis due to early lethality, however, when granulosa cell tumors are removed at 6 weeks of age, mice show development of large lung metastases 6-16 weeks later, indicating that tumors indeed are metastatic (J:142150)

• 44% of mice develop pulmonary metastases by 4 months (J:149060)

reproductive system

increased ovary tumor incidence ( J:142150 )

♀ • presence of nests of dysplastic cells are seen in the ovaries of newborn mice and E20.5, but not E18.5, indicating that tumor growth begins perinatally

increased granulosa cell tumor incidence ( J:149060 )

• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age

seminiferous tubule degeneration ( J:149060 )

♂ • seminiferous tubule degeneration is seen by 3 weeks of age

increased testis tumor incidence ( J:149060 )

♂ • 100% penetrance of aggressive testicular cancer

♂ • tumors are first observable at 5 weeks of age, and by 3 months of age, about 70% of mice have unilateral testicular tumors and 30% have bilateral tumors

♂ • tumors exhibit characteristics of granulosa cell tumors of the testis and not Sertoli cell tumors

endocrine/exocrine glands

increased ovary tumor incidence ( J:142150 )

♀ • presence of nests of dysplastic cells are seen in the ovaries of newborn mice and E20.5, but not E18.5, indicating that tumor growth begins perinatally

increased granulosa cell tumor incidence ( J:149060 )

• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age

seminiferous tubule degeneration ( J:149060 )

♂ • seminiferous tubule degeneration is seen by 3 weeks of age

increased testis tumor incidence ( J:149060 )

♂ • 100% penetrance of aggressive testicular cancer

♂ • tumors are first observable at 5 weeks of age, and by 3 months of age, about 70% of mice have unilateral testicular tumors and 30% have bilateral tumors

♂ • tumors exhibit characteristics of granulosa cell tumors of the testis and not Sertoli cell tumors

cardiovascular system

pulmonary embolism ( J:142150 )

• pulmonary tumor cell embolisms

hematopoietic system

extramedullary hematopoiesis ( J:142150 )

• extrensive extramedullary hematopoiesis

anemia ( J:142150 )

• severe anemia

decreased hematocrit ( J:142150 )

mortality/aging

premature death ( J:142150 )

• female mice die before 9 weeks of age

respiratory system

pulmonary embolism ( J:142150 )

• pulmonary tumor cell embolisms

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
granulosa cell tumor		DOID:2999		J:142150
testicular granulosa cell tumor		DOID:5331		J:149060

Genotype
MGI:5432232

cn77

• Allelic Composition: Amhr2^tm3(cre)Bhr/Amhr2⁺; Ctnnb1^tm1Mmt/Ctnnb1⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6

neoplasm

increased granulosa cell tumor incidence ( J:186144 )

♀ • female mutants develop granulosa cell tumors by 3 weeks of age

increased testis tumor incidence ( J:186144 )

♂ • male mutants develop testicular granulosa cell tumors by 5 weeks of age

endocrine/exocrine glands

increased granulosa cell tumor incidence ( J:186144 )

♀ • female mutants develop granulosa cell tumors by 3 weeks of age

increased testis tumor incidence ( J:186144 )

♂ • male mutants develop testicular granulosa cell tumors by 5 weeks of age

reproductive system

increased granulosa cell tumor incidence ( J:186144 )

♀ • female mutants develop granulosa cell tumors by 3 weeks of age

increased testis tumor incidence ( J:186144 )

♂ • male mutants develop testicular granulosa cell tumors by 5 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
granulosa cell tumor		DOID:2999		J:186144
juvenile type testicular granulosa cell tumor		DOID:6032		J:186144
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:186144

Genotype
MGI:5013567

cn78

• Allelic Composition: Amhr2^tm3(cre)Bhr/Amhr2⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6

reproductive system

reproductive system phenotype ( J:187754 )

♂N • no abnormalities in testis

abnormal maternal decidual layer morphology ( J:170203 )

♀ • mean mutant mesometrial maternal decidua surface area is 2.81-fold greater than in controls

♀ • decidua are abnormal in appearance, featuring many mitotic figures in females 11.5 days pregnant, with little evidence of apoptosis, and many cells with unusually abundant cytoplasm, particularly near the trophoblast invasion front

♀ • 9-fold decrease in apoptotic decidaul cells in mutants relative to controls

♀ • about 2-3 days after expected parturition in the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma

♀ • these results indicate failure of decidual regression

decreased uterine NK cell number ( J:170203 )

♀ • mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc

abnormal endometrium morphology ( J:170203 )

♀ • endometrium epithelial cells appear hypertrophic, hyperplastic, and disorganized

♀ • about 2-3 days after expected parturition of the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma

endometrium fibrosis ( J:170203 )

♀ • endometrial fibrosis is seen in females beyond the first gestation at day 112.5 and day 119.45 pc

endometrium hyperplasia ( J:170203 )

♀

abnormal myometrium morphology ( J:170203 )

♀ • thickening of the myometrium and disorganization of the muscle fibers before and throughout gestation

uterus hyperplasia ( J:170203 )

♀ • uteri of pregnant females beyond the first gestation, show varying degrees of hyperplasia of both the uterine and glandular epithelia

reduced female fertility ( J:170203 )

♀ • primiparous females exhibit reduced fertility due to increased fetal loss at E11.5

♀ • almost all mutant females fail to carry a second litter to term; females pregnant for the second time show signs of implantation but no viable fetuses at 9.5 dpc

decreased litter size ( J:170203 )

• females produce about 44% fewer pups per mating than controls

• implanted fetuses fail to develop to term due to epithelial hyperplasia and other uterine anomalies

embryo

abnormal placenta vasculature ( J:170203 )

♀ • females at 11.5 days of pregnancy exhibit poorly transformed maternal vasculature in the decidua, showing persistence of the muscular layer of maternal vessels, even deep within the decidual tissue, however maternal vascular transformation appears complete by 14.5 dpc, indicating a transient delay in vasculature transformation

abnormal maternal decidual layer morphology ( J:170203 )

♀ • mean mutant mesometrial maternal decidua surface area is 2.81-fold greater than in controls

♀ • decidua are abnormal in appearance, featuring many mitotic figures in females 11.5 days pregnant, with little evidence of apoptosis, and many cells with unusually abundant cytoplasm, particularly near the trophoblast invasion front

♀ • 9-fold decrease in apoptotic decidaul cells in mutants relative to controls

♀ • about 2-3 days after expected parturition in the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma

♀ • these results indicate failure of decidual regression

decreased uterine NK cell number ( J:170203 )

♀ • mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc

abnormal placenta labyrinth morphology ( J:170203 )

♀ • abnormal development of the placental labyrinth, and frequent apparent intrauterine fetal growth restriction

♀ • by 11.5 dpc, the placental labyrinth is thin and underdeveloped in most concepti of mutant females

abnormal trophoblast layer morphology ( J:170203 )

• by 11.5 dpc, trophoblast migration appears restricted by an abnormally thick maternal decidua

• fetal trophoblast glycogen cells do not migrate beyond the parietal trophoblast giant cell border by 14.5 dpc as in controls and are halted at the maternal-fetal interface

• trophoblast migration is impeded by inhibition of decidual regression and is attributable to inhibition of decidual cell apoptosis

immune system

decreased uterine NK cell number ( J:170203 )

♀ • mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc

hematopoietic system

decreased uterine NK cell number ( J:170203 )

♀ • mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc

cardiovascular system

abnormal placenta vasculature ( J:170203 )

♀ • females at 11.5 days of pregnancy exhibit poorly transformed maternal vasculature in the decidua, showing persistence of the muscular layer of maternal vessels, even deep within the decidual tissue, however maternal vascular transformation appears complete by 14.5 dpc, indicating a transient delay in vasculature transformation

endocrine/exocrine glands

decreased uterine NK cell number ( J:170203 )

♀ • mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc

Genotype
MGI:5432226

cn79

• Allelic Composition: Ctnnb1^tm1Mmt/Ctnnb1⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(CYP19A1-cre)1Jri/0
• Genetic Background: involves: 129S4/SvJae * 129X1/SvJ * C57BL/6

mortality/aging

decreased tumor-free survival time ( J:186144 )

• all mutants die within 2-3 months of age due to tumor burden

neoplasm

increased ovary tumor incidence ( J:186144 )

♀ • mutants exhibit precancerous lesions in the ovaries by 3 weeks of age

increased granulosa cell tumor incidence ( J:186144 )

♀ • mutants develop large granulosa cell tumors by 6-8 weeks of age

endocrine/exocrine glands

decreased granulosa cell apoptosis ( J:186144 )

♀ • granulosa cell apoptosis is decreased in the ovaries at 5-6 weeks of age

impaired granulosa cell differentiation ( J:186144 )

♀ • marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked

increased granulosa cell proliferation ( J:186144 )

♀ • granulosa cell proliferation is increased in the ovaries at 5-6 weeks of age

increased ovary tumor incidence ( J:186144 )

♀ • mutants exhibit precancerous lesions in the ovaries by 3 weeks of age

increased granulosa cell tumor incidence ( J:186144 )

♀ • mutants develop large granulosa cell tumors by 6-8 weeks of age

reproductive system

decreased granulosa cell apoptosis ( J:186144 )

♀ • granulosa cell apoptosis is decreased in the ovaries at 5-6 weeks of age

impaired granulosa cell differentiation ( J:186144 )

♀ • marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked

increased granulosa cell proliferation ( J:186144 )

♀ • granulosa cell proliferation is increased in the ovaries at 5-6 weeks of age

increased ovary tumor incidence ( J:186144 )

♀ • mutants exhibit precancerous lesions in the ovaries by 3 weeks of age

increased granulosa cell tumor incidence ( J:186144 )

♀ • mutants develop large granulosa cell tumors by 6-8 weeks of age

homeostasis/metabolism

decreased circulating estradiol level ( J:186144 )

• by 6 weeks of age

increased circulating follicle stimulating hormone level ( J:186144 )

• by 6 weeks of age

increased circulating luteinizing hormone level ( J:186144 )

• by 6 weeks of age

decreased circulating progesterone level ( J:186144 )

• by 6 weeks of age

cellular

decreased granulosa cell apoptosis ( J:186144 )

♀ • granulosa cell apoptosis is decreased in the ovaries at 5-6 weeks of age

impaired granulosa cell differentiation ( J:186144 )

♀ • marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked

increased granulosa cell proliferation ( J:186144 )

♀ • granulosa cell proliferation is increased in the ovaries at 5-6 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
granulosa cell tumor		DOID:2999		J:186144
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:186144

Genotype
MGI:4943270

cn80

• Allelic Composition: Ctnnb1^tm1Mmt/Ctnnb1⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Upk2-cre)6Xrw/0
• Genetic Background: involves: 129S4/SvJae * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:164579 )

neoplasm

increased urinary bladder carcinoma incidence ( J:164579 )

• mice develop urothelial bladder tumors that progress to papillary carcinoma

renal/urinary system

increased urinary bladder carcinoma incidence ( J:164579 )

• mice develop urothelial bladder tumors that progress to papillary carcinoma

Genotype
MGI:4943268

cn81

• Allelic Composition: Ctnnb1^tm1Mmt/Ctnnb1^tm1Mmt; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Upk2-cre)6Xrw/0
• Genetic Background: involves: 129S4/SvJae * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:164579 )

neoplasm

increased urinary bladder carcinoma incidence ( J:164579 )

• mice develop urothelial bladder tumors that progress to papillary carcinoma

renal/urinary system

increased urinary bladder carcinoma incidence ( J:164579 )

• mice develop urothelial bladder tumors that progress to papillary carcinoma

Genotype
MGI:5517675

cn82

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

endocrine/exocrine glands

abnormal thyroid follicle morphology ( J:197590 )

• enlarged follicles

enlarged thyroid gland ( J:197590 )

• mutants have an enlarged thyroid at 2 years of age and exhibit a goiter-like phenotype, but do not show development of tumors

thyroid gland hyperplasia ( J:197590 )

homeostasis/metabolism

increased thyroxine level ( J:197590 )

• P14 mutants show an increase in T4 levels

Genotype
MGI:5014514

cn83

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:197590 )

N • Background Sensitivity: unlike on the congenic C57BL/6 background, mutants on the BALB/c background have normal T4 and TSH levels

decreased susceptibility to injury ( J:167962 )

• after naphthalene administration to induce lung injury, the proximal airway epithelium at 3 and 7 days post injury appears intact with no signs of injury

• after naphthalene administration to induce lung injury, the level of injury in the bronchial airway epithelium is reduced and repair is enhanced compared to controls

respiratory system

increased lung endothelial cell proliferation ( J:167962 )

• mutants exhibit an increase in the proliferation rate of the epithelial cells in E15.5 lungs

• expansion of epithelial cell populations occurs in multiple progenitor cell niches of the lungs including the tracheal basal cells in the proximal lung, the neuroepithelial bodies (NEB) in the distal bronchi and the progenitor cells occupying the bronchioalveolarduct junction (BADJ) region

abnormal lung morphology ( J:167962 )

• lungs exhibit increased cell proliferation and decreased apoptosis

• lungs at 8 weeks of age sometimes contain a mass consisting of epithelial cells (putative progenitor cell masses) around the BADJ area; masses are slow growing and are organized into ductlike structures

pulmonary hyperplasia ( J:167962 )

• progressive epithelial hyperplasia extending from the trachea to the small bronchioles is seen in the proximal lung epithelium from early stages of lung development and in adults

abnormal lung development ( J:167962 )

• marker analysis indicates a block in transition from precursor to terminally differentiated cell types indicating impaired epithelial cell fate determination in the lung

increased club cell number ( J:167962 )

• increase in number of Clara cells in the lungs and a decrease in the number of ciliated cells, the terminally differentiated progeny of Clara cells

cellular

increased lung endothelial cell proliferation ( J:167962 )

• mutants exhibit an increase in the proliferation rate of the epithelial cells in E15.5 lungs

• expansion of epithelial cell populations occurs in multiple progenitor cell niches of the lungs including the tracheal basal cells in the proximal lung, the neuroepithelial bodies (NEB) in the distal bronchi and the progenitor cells occupying the bronchioalveolarduct junction (BADJ) region

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:197590 )

• Background Sensitivity: at P14, epithelial cell proliferation rates in the thyroid are lower on the mixed BALB/c background than on the congenic C57BL/6 background

• at P14, thyroid architecture is conserved but an increase in the number of epithelial cells along the follicles is seen, resembling a goiter disease

enlarged thyroid gland ( J:197590 )

thyroid gland hyperplasia ( J:197590 )

mortality/aging

mortality/aging ( J:197590 )

N • Background Sensitivity: mutants survive to adulthood on the BALB/c background without presenting any obvious pathological conditions unlike mice on the congenic C57BL/6 background

growth/size/body

pulmonary hyperplasia ( J:167962 )

• progressive epithelial hyperplasia extending from the trachea to the small bronchioles is seen in the proximal lung epithelium from early stages of lung development and in adults

Genotype
MGI:5013916

cn84

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten⁺; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

neoplasm

increased pancreas tumor incidence ( J:164210 )

• mutants exhibit accelerated development of acinar-to-ductal metaplasia, malignant pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma compared to single heterozygous Kras mutants, with almost 100% of mutants succumbing to cancer by 12 months of age

• 21 of 25 mice alive past 2 months of age develop well-to-moderately differentiated invasive ductal cancers

• rare metastasis to lungs is seen

increased pancreatic ductal adenocarcinoma incidence ( J:164210 )

• at 3 months of age, 8 of 12 mutants show development of pancreatic ductal adenocarcinoma (PDAC), and all mice show PDAC by 6 months of age

• loss of Pten heterozygosity is seen during pancreatic ductal adenocarcinoma progression but not in mPanIN lesions

increased pancreatic intraepithelial neoplasia incidence ( J:164210 )

• mutants show malignant pancreatic intraepithelial neoplasia (mPanIN) development starting at 1 month of age, and all show mPanIN by 3 months of age

mortality/aging

premature death ( J:164210 )

• median survival time is about 3.5 months

endocrine/exocrine glands

increased pancreas tumor incidence ( J:164210 )

• mutants exhibit accelerated development of acinar-to-ductal metaplasia, malignant pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma compared to single heterozygous Kras mutants, with almost 100% of mutants succumbing to cancer by 12 months of age

• 21 of 25 mice alive past 2 months of age develop well-to-moderately differentiated invasive ductal cancers

• rare metastasis to lungs is seen

increased pancreatic ductal adenocarcinoma incidence ( J:164210 )

• at 3 months of age, 8 of 12 mutants show development of pancreatic ductal adenocarcinoma (PDAC), and all mice show PDAC by 6 months of age

• loss of Pten heterozygosity is seen during pancreatic ductal adenocarcinoma progression but not in mPanIN lesions

increased pancreatic intraepithelial neoplasia incidence ( J:164210 )

• mutants show malignant pancreatic intraepithelial neoplasia (mPanIN) development starting at 1 month of age, and all show mPanIN by 3 months of age

pancreatic acinar-to-ductal metaplasia ( J:164210 )

• acinar-to-ductal metaplasia is seen at 1-3 months of age, concentrated in the transition zone between morphologically normal pancreatic structures and mPanIN and PDAC lesions

• acinar-to-ductal metaplasia development precedes mPanIN formation

• metaplastic lesions show an increase in CD44+ cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:164210

Genotype
MGI:5013917

cn85

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6 * CBA

neoplasm

increased pancreatic ductal adenocarcinoma incidence ( J:164210 )

• all mutants develop pancreatic ductal adenocarcinoma by 3 weeks of age

increased pancreatic intraepithelial neoplasia incidence ( J:164210 )

endocrine/exocrine glands

abnormal exocrine pancreas morphology ( J:164210 )

• mutants show severe exocrine pancreatic atrophy and edema along with the presence of mPanINs, metaplasias, and ducto-insular complexes and pancreatic ductal adenocarcinoma at P17

exocrine pancreas atrophy ( J:164210 )

• severe

increased pancreatic ductal adenocarcinoma incidence ( J:164210 )

• all mutants develop pancreatic ductal adenocarcinoma by 3 weeks of age

increased pancreatic intraepithelial neoplasia incidence ( J:164210 )

pancreatic acinar-to-ductal metaplasia ( J:164210 )

• mutants exhibit acinar-to-ductal metaplasia

homeostasis/metabolism

edema ( J:164210 )

• pancreas at P1-P17 shows edema

mortality/aging

postnatal lethality, complete penetrance ( J:164210 )

• mutants are moribound by weaning, with a median survival of about 17 days

digestive/alimentary system

abnormal exocrine pancreas morphology ( J:164210 )

• mutants show severe exocrine pancreatic atrophy and edema along with the presence of mPanINs, metaplasias, and ducto-insular complexes and pancreatic ductal adenocarcinoma at P17

exocrine pancreas atrophy ( J:164210 )

• severe

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:164210

Genotype
MGI:5008144

cn86

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:170129 )

• beta-cell size is increased by 15% compared to controls

• number of proliferating beta-cells is increased by 34% compared to controls

increased pancreatic beta cell mass ( J:170129 )

• beta-cell mass is 86% higher than controls after adjusting for body size

• however, pancreatic insulin content is unchanged and insulin sensitivity is normal

growth/size/body

postnatal growth retardation ( J:170129 )

Genotype
MGI:4847617

cn87

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(CAG-fat-1)1Jxk/0; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2

endocrine/exocrine glands

decreased prostate gland weight ( J:124208 )

♂ • mice fed a high-omega-6 diet exhibit significantly lower prostate weights than mice without Tg(CAG-fat-1)1Jxk

homeostasis/metabolism

abnormal lipid homeostasis ( J:124208 )

• mice fed a high-omega-6 diet exhibit a much lower omega-6/omega-3 ratio in the blood and prostate than mice without the Tg(CAG-fat-1)1Jxk transgene, indicating that fat-1 is able to convert most of the omega-6 polyunsaturated fatty acids to omega-3

reproductive system

decreased prostate gland weight ( J:124208 )

♂ • mice fed a high-omega-6 diet exhibit significantly lower prostate weights than mice without Tg(CAG-fat-1)1Jxk

Genotype
MGI:4843916

cn88

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(ARR2/Pbsn-FGF8)3Prb/0; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2

endocrine/exocrine glands

prostate gland epithelial hyperplasia ( J:106650 )

♂

enlarged prostate gland ( J:106650 )

♂ • enlarged prostate gland due to epithelial hyperplasia

increased prostate gland adenocarcinoma incidence ( J:106650 )

♂ • prostatic adenocarcinomas are seen from 9 months onward

♂ • adenocarcinomas are seen in all lobes, although more often in the dorsolateral and ventral lobes than anterior lobes

♂ • 6 of 17 mutants at 9-16.2 months of age and 9 of 10 mutants at 18.2-19.1 months exhibit adenocarcinomas

♂ • adenocarcinomas show loss of heterozygosity of Pten

♂ • 2 of 31 mutants develop a rare form of mucinous adenocarcinoma

increased prostate intraepithelial neoplasia incidence ( J:106650 )

♂ • males by 6.5 months of age exhibit hyperplasia and focal-low grade PIN lesions in the prostate

♂ • males older than 7.5 months of age exhibit high-grade PINs

reproductive system

prostate gland epithelial hyperplasia ( J:106650 )

♂

enlarged prostate gland ( J:106650 )

♂ • enlarged prostate gland due to epithelial hyperplasia

increased prostate gland adenocarcinoma incidence ( J:106650 )

♂ • prostatic adenocarcinomas are seen from 9 months onward

♂ • adenocarcinomas are seen in all lobes, although more often in the dorsolateral and ventral lobes than anterior lobes

♂ • 6 of 17 mutants at 9-16.2 months of age and 9 of 10 mutants at 18.2-19.1 months exhibit adenocarcinomas

♂ • adenocarcinomas show loss of heterozygosity of Pten

♂ • 2 of 31 mutants develop a rare form of mucinous adenocarcinoma

increased prostate intraepithelial neoplasia incidence ( J:106650 )

♂ • males by 6.5 months of age exhibit hyperplasia and focal-low grade PIN lesions in the prostate

♂ • males older than 7.5 months of age exhibit high-grade PINs

neoplasm

increased prostate gland adenocarcinoma incidence ( J:106650 )

♂ • prostatic adenocarcinomas are seen from 9 months onward

♂ • adenocarcinomas are seen in all lobes, although more often in the dorsolateral and ventral lobes than anterior lobes

♂ • 6 of 17 mutants at 9-16.2 months of age and 9 of 10 mutants at 18.2-19.1 months exhibit adenocarcinomas

♂ • adenocarcinomas show loss of heterozygosity of Pten

♂ • 2 of 31 mutants develop a rare form of mucinous adenocarcinoma

increased prostate intraepithelial neoplasia incidence ( J:106650 )

♂ • males by 6.5 months of age exhibit hyperplasia and focal-low grade PIN lesions in the prostate

♂ • males older than 7.5 months of age exhibit high-grade PINs

increased metastatic potential ( J:106650 )

• metastasis of adenocarcionma into lymph nodes is observed, with 50-60% penetrance

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:106650

Genotype
MGI:4420975

cn89

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:93902 )

♂ • latency to prostate intraepithelial neoplasia is 8 to 10 months

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:93902 )

♂ • latency to prostate intraepithelial neoplasia is 8 to 10 months

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:93902 )

♂ • latency to prostate intraepithelial neoplasia is 8 to 10 months

Genotype
MGI:4420974

cn90

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2

mortality/aging

premature death ( J:93902 )

• 3 of 14 mice die by age 12 to 29 weeks

• however, all castrated mice survive from 7 to 10 months

decreased tumor-free survival time ( J:124208 )

• 12 month survival rate of mutants is 60% on the high-omega-3 diet, 10% on the low-omega-3 diet and 0% on the high-omega-6 diet

• mutants on a high-omega-6 diet do not survive beyond 10 months of age and die due to bladder obstruction by the prostate tumor compressing the urethra

reproductive system

abnormal prostate gland morphology ( J:124208 )

♂ • prostate lobes are enlarged and exhibit increased vascularity and cellularity

abnormal prostate gland epithelium morphology ( J:93902 )

♂ • at 4 weeks, epithelium cells in the lateral prostate are larger than in Pten^tm1Hwu homozygotes

prostate gland epithelial hyperplasia ( J:93902 )

♂ • without cellular atypia by 4 weeks of age

enlarged prostate gland ( J:93902 )

♂ • mice exhibit progressive enlargement of the prostate gland compared to in Pten^tm1Hwu homozygotes

♂ • however, castration reduces prostate size

increased prostate gland weight ( J:124208 )

♂ • prostate weight is higher than in controls starting at 8 weeks of age

♂ • prostate weight gain from 5 to 24 weeks is significantly less in mice fed a high-omega-3 diet than in mice fed a high-omega-6 diet

prostate gland hyperplasia ( J:93902 )

♂ • at 4 weeks, mice develop multifocal hyperplasia compared to in Pten^tm1Hwu homozygotes

♂ • hyperplasia is initially observed in the dorsolateral and ventral lobe with subsequent involvement of the anterior lobes

increased prostate gland tumor incidence ( J:124208 )

♂ • males develop prostate cancer

increased prostate gland adenocarcinoma incidence ( J:93902 , J:124208 )

♂ • mice develop invasive adenocarcinoma by 9 weeks of age in all lobes (J:93902)

♂ • prostate cancers are metastatic (J:93902)

♂ • castrated mice still develop invasive adenocarcinoma (J:93902)

♂ • 80% of mutants fed a high-omega-6 diet develop invasive carcinoma while 50% of mutants fed a high-omega-3 diet develop invasive carcinoma (J:124208)

increased prostate intraepithelial neoplasia incidence ( J:93902 , J:106650 )

♂ • by 6 weeks of age, all mice develop prostate intraepithelial neoplasia (J:93902)

♂ • latency to prostate intraepithelial neoplasia is 1.5 months (J:93902)

♂ • males develop PIN lesions after 16 months of age (J:106650)

abnormal prostate gland physiology ( J:93902 , J:124208 )

♂ • prostate cancer cells exhibit increased proliferation compared to in Pten^tm1Hwu homozygotes (J:93902)

♂ • cancer cells induce a desmoplastic response (J:93902)

♂ • castrated mice exhibit increased proliferation compared with similarly treated Pten^tm1Hwu homozygotes (J:93902)

♂ • higher numbers of apoptotic cells are seen in mutant prostates from mice on the high-omega-3 diet than on the high-omega-6 diet (J:124208)

prostate gland inflammation ( J:93902 )

♂ • cancer cells induce inflammation

neoplasm

increased prostate gland tumor incidence ( J:124208 )

♂ • males develop prostate cancer

increased prostate gland adenocarcinoma incidence ( J:93902 , J:124208 )

♂ • prostate cancers are metastatic (J:93902)

♂ • castrated mice still develop invasive adenocarcinoma (J:93902)

♂ • mice develop invasive adenocarcinoma by 9 weeks of age in all lobes (J:93902)

♂ • 80% of mutants fed a high-omega-6 diet develop invasive carcinoma while 50% of mutants fed a high-omega-3 diet develop invasive carcinoma (J:124208)

increased prostate intraepithelial neoplasia incidence ( J:93902 , J:106650 )

♂ • by 6 weeks of age, all mice develop prostate intraepithelial neoplasia (J:93902)

♂ • latency to prostate intraepithelial neoplasia is 1.5 months (J:93902)

♂ • males develop PIN lesions after 16 months of age (J:106650)

decreased tumor incidence ( J:124208 )

• omega-3 polyunsaturated fatty acids (PUFAs) slow the progression of prostate tumors in 5- to 8-week old mutants; once carcinoma develops, omega-3 PUFAs induce apoptosis and decrease the growth of the tumor

immune system

prostate gland inflammation ( J:93902 )

♂ • cancer cells induce inflammation

pyelonephritis ( J:124208 )

• mutants surviving 6 months or longer exhibit pyelonephritis

endocrine/exocrine glands

abnormal prostate gland morphology ( J:124208 )

♂ • prostate lobes are enlarged and exhibit increased vascularity and cellularity

abnormal prostate gland epithelium morphology ( J:93902 )

♂ • at 4 weeks, epithelium cells in the lateral prostate are larger than in Pten^tm1Hwu homozygotes

prostate gland epithelial hyperplasia ( J:93902 )

♂ • without cellular atypia by 4 weeks of age

enlarged prostate gland ( J:93902 )

♂ • mice exhibit progressive enlargement of the prostate gland compared to in Pten^tm1Hwu homozygotes

♂ • however, castration reduces prostate size

increased prostate gland weight ( J:124208 )

♂ • prostate weight is higher than in controls starting at 8 weeks of age

♂ • prostate weight gain from 5 to 24 weeks is significantly less in mice fed a high-omega-3 diet than in mice fed a high-omega-6 diet

prostate gland hyperplasia ( J:93902 )

♂ • at 4 weeks, mice develop multifocal hyperplasia compared to in Pten^tm1Hwu homozygotes

♂ • hyperplasia is initially observed in the dorsolateral and ventral lobe with subsequent involvement of the anterior lobes

increased prostate gland tumor incidence ( J:124208 )

♂ • males develop prostate cancer

increased prostate gland adenocarcinoma incidence ( J:93902 , J:124208 )

♂ • mice develop invasive adenocarcinoma by 9 weeks of age in all lobes (J:93902)

♂ • prostate cancers are metastatic (J:93902)

♂ • castrated mice still develop invasive adenocarcinoma (J:93902)

♂ • 80% of mutants fed a high-omega-6 diet develop invasive carcinoma while 50% of mutants fed a high-omega-3 diet develop invasive carcinoma (J:124208)

increased prostate intraepithelial neoplasia incidence ( J:93902 , J:106650 )

♂ • by 6 weeks of age, all mice develop prostate intraepithelial neoplasia (J:93902)

♂ • latency to prostate intraepithelial neoplasia is 1.5 months (J:93902)

♂ • males develop PIN lesions after 16 months of age (J:106650)

abnormal prostate gland physiology ( J:93902 , J:124208 )

♂ • prostate cancer cells exhibit increased proliferation compared to in Pten^tm1Hwu homozygotes (J:93902)

♂ • cancer cells induce a desmoplastic response (J:93902)

♂ • castrated mice exhibit increased proliferation compared with similarly treated Pten^tm1Hwu homozygotes (J:93902)

♂ • higher numbers of apoptotic cells are seen in mutant prostates from mice on the high-omega-3 diet than on the high-omega-6 diet (J:124208)

prostate gland inflammation ( J:93902 )

♂ • cancer cells induce inflammation

renal/urinary system

abnormal renal/urinary system physiology ( J:124208 )

• mutants surviving 6 months or longer exhibit retention of urine in the anterior prostate lobes

pyelonephritis ( J:124208 )

• mutants surviving 6 months or longer exhibit pyelonephritis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:93902

Genotype
MGI:4839560

cn91

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Cdh5-cre)7Mlia/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6 * FVB/N

hematopoietic system

enlarged thymus ( J:135172 )

• 70% of mutants exhibit enlarged thymus

enlarged spleen ( J:135172 )

• splenomegaly

abnormal definitive hematopoiesis ( J:135172 )

• progressive development of myeloproliferative disorder and leukemogenesis in the chronic phase followed by blast crisis

increased leukocyte cell number ( J:135172 )

• 2-3 months after birth, mutants show increased circulating neutrophils and white blood cells and leukemic blast invasion into hematopoietic and non-hematopoietic organs

increased neutrophil cell number ( J:135172 )

• one month after birth, mutants develop a myeloid shift with increased neutrophil counts

immune system

enlarged thymus ( J:135172 )

• 70% of mutants exhibit enlarged thymus

enlarged spleen ( J:135172 )

• splenomegaly

increased leukocyte cell number ( J:135172 )

• 2-3 months after birth, mutants show increased circulating neutrophils and white blood cells and leukemic blast invasion into hematopoietic and non-hematopoietic organs

increased neutrophil cell number ( J:135172 )

• one month after birth, mutants develop a myeloid shift with increased neutrophil counts

enlarged lymph nodes ( J:135172 )

• 70% of mutants exhibit enlarged lymph nodes

liver/biliary system

enlarged liver ( J:135172 )

• hepatomegaly

neoplasm

increased acute lymphoblastic leukemia incidence ( J:135172 )

• 74% of mutants develop T-lymphoblastic leukemia

increased acute promyelocytic leukemia incidence ( J:135172 )

• 26% of mutants develop acute myeloid leukemia

endocrine/exocrine glands

enlarged thymus ( J:135172 )

• 70% of mutants exhibit enlarged thymus

growth/size/body

enlarged liver ( J:135172 )

• hepatomegaly

enlarged spleen ( J:135172 )

• splenomegaly

Genotype
MGI:4942301

cn92

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Camk2a-cre)T50Stl/0; Tg(Thy1-EGFP)MJrs/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6J * CBA

nervous system

increased brain size ( J:145970 )

• increase in brain size due to expansion of allocortex and neocortex

abnormal dendrite morphology ( J:145970 )

• apical dendrites of pyramidal neurons in cortical layer 2/3 but not layer 5 are longer and more tortuous than in controls

• total arbor length is on average 1.6 mm longer in mutants, indicating an approximate 80% expansion of the apical dendritic tree

• however, basal dendritic length is not different

• rapamycin treatments completely prevent dendritic growth seen following Pten deletion

Genotype
MGI:4943534

cn93

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Vhl^tm1Jae/Vhl^tm1Jae; Tg(Cdh16-cre)91Igr/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6J * ICR

renal/urinary system

increased kidney cell proliferation ( J:137073 )

• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex

kidney cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney cortex and medulla

• cysts develop in all mice (14 of 14) and are seen as early as 6-8 weeks of age

• cysts arise in collecting ducts and distal tubules

• most cysts are lined by a single layer of epithelial cells (simple cysts), whereas ~8% of cysts are lined by multilayered epithelial cells with occasional papillary projections (atypical cysts)

• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type

kidney cortex cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney cortex

kidney medulla cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney medulla

increased kidney weight ( J:137073 )

• males and females exhibit enlarged and heavier kidneys due to epithelial tubule cysts

abnormal kidney cortex morphology ( J:137073 )

• 3 of 14 mice show isolated regions of benign squamous metaplasia within the kidney cortex

abnormal kidney epithelium morphology ( J:137073 )

• kidney epithelial cells fail to maintain their primary cilia, resulting in uncontrolled proliferation and cyst formation

abnormal renal tubule epithelial cell primary cilium morphology ( J:137073 )

• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type

abnormal kidney pelvis urothelium morphology ( J:137073 )

• hyperproliferation of the urothelium in the renal pelvis is more pronounced than in single Pten mutants

hydronephrosis ( J:137073 )

cellular

abnormal renal tubule epithelial cell primary cilium morphology ( J:137073 )

• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type

increased kidney cell proliferation ( J:137073 )

• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex

neoplasm

neoplasm ( J:137073 )

N • no tumors areas seen at 3-6 months of age, when mice are euthanized to avoid renal failure

growth/size/body

kidney cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney cortex and medulla

• cysts develop in all mice (14 of 14) and are seen as early as 6-8 weeks of age

• cysts arise in collecting ducts and distal tubules

• most cysts are lined by a single layer of epithelial cells (simple cysts), whereas ~8% of cysts are lined by multilayered epithelial cells with occasional papillary projections (atypical cysts)

• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type

kidney cortex cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney cortex

kidney medulla cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney medulla

increased kidney weight ( J:137073 )

• males and females exhibit enlarged and heavier kidneys due to epithelial tubule cysts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
von Hippel-Lindau disease		DOID:14175	OMIM:193300	J:137073

Genotype
MGI:4943546

cn94

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Cdh16-cre)91Igr/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6J * ICR

renal/urinary system

renal/urinary system phenotype ( J:137073 )

N • mutants do not develop hydronephrosis

abnormal ureter morphology ( J:137073 )

• hyperproliferation and enlarged epithelial cells in the ureter

abnormal urinary bladder urothelium morphology ( J:137073 )

• hyperproliferation and enlarged epithelial cells in the bladder

Genotype
MGI:4941760

cn95

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6J * SJL

digestive/alimentary system

abnormal small intestinal crypt cell proliferation ( J:150553 )

• increase in crypt cell proliferation

abnormal intestine morphology ( J:150553 )

• intestine is 1.28-fold longer and weighs 1.58-fold more than controls

• however, mutants do not develop polyps

abnormal intestinal mucosa morphology ( J:150553 )

• thickening of the intestinal mucosa

abnormal intestinal goblet cell morphology ( J:150553 )

• increase in the number and size of goblet cells

abnormal intestinal enteroendocrine cell morphology ( J:150553 )

• decrease in the number of enteroendocrine cells

abnormal small intestine morphology ( J:150553 )

• thickening of the muscular layers of the small intestine

abnormal small intestine crypts of Lieberkuhn morphology ( J:150553 )

• small intestine exhibits an expanded crypt compartment with increased number of crypts per villus

abnormal Paneth cell morphology ( J:150553 )

• marker analysis indicates impaired Paneth cell maturation

abnormal duodenum morphology ( J:150553 )

• total protein content of the duodenum is enhanced by 50%

abnormal jejunum morphology ( J:150553 )

• jejunum exhibits expanded crypt and villus compartments, an increased number of crypts, thickening of the muscular layers and villus branching

abnormal small intestinal villus morphology ( J:150553 )

• small intestine exhibits an expanded villus compartment

branched small intestinal villi ( J:150553 )

• mutants exhibit branching of the villi in the small intestine

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:150553 )

• small intestine exhibits an expanded crypt compartment with increased number of crypts per villus

abnormal Paneth cell morphology ( J:150553 )

• marker analysis indicates impaired Paneth cell maturation

cellular

abnormal intestinal goblet cell morphology ( J:150553 )

• increase in the number and size of goblet cells

abnormal small intestinal crypt cell proliferation ( J:150553 )

• increase in crypt cell proliferation

Genotype
MGI:4941759

cn96

• Allelic Composition: Apc^Min/Apc⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6J * SJL

mortality/aging

premature death ( J:150553 )

• all mutants die within 80 days

neoplasm

increased intestinal adenoma incidence ( J:150553 )

• adenomas in the small intestine

digestive/alimentary system

increased intestinal adenoma incidence ( J:150553 )

• adenomas in the small intestine

intestine polyps ( J:150553 )

• mutants develop an average of 20.1 intestinal polyps per mouse, an 11.17-fold increase over the numbers seen in heterozygous Apc mice

Genotype
MGI:3838843

cn97

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Gfap-cre)77.6Mvs/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6NHsd

nervous system

abnormal neuron differentiation ( J:146630 )

• cultured adult neural stem cells maintain their ability to differentiate into neurons for a longer time compared to wild-type cells

abnormal neuronal precursor proliferation ( J:146630 )

• in culture, neurospheres formed by adult neural stem cells are generally larger and the stem cells' capacity for self renewal is prolonged compared to wild-type cells

abnormal response to CNS ischemic injury ( J:146630 )

• 7 days after induction of limited stroke in the sensorimotor cortex, mice have more neuroblasts in the peri-infarct cortex compared to controls

• however, there is no difference in the number of new cells present at 90 days after stroke induction

abnormal olfactory bulb morphology ( J:146630 )

• continuous increase in the weight and size of the olfactory bulb compared to controls starting at 2.5 months of age

• the granule cell layer volume is increased 2 fold at 3.5 months of age

• the increase in volume is due to an increase in the number of cells migrating from the subependymal zone to the olfactory bulb and a decrease in the number of apoptotic cells in the granule cell layer

abnormal postnatal subventricular zone morphology ( J:146630 )

• increase in the volume of the subependymal zone compared to controls

• increase in the number of proliferating cells and DCX positive neuroblasts

increased neuronal precursor cell number ( J:146630 )

• expansion of the adult neural stem cell and progenitor populations in the subependymal zone

behavior/neurological

abnormal response to novel odor ( J:146630 )

• habituate faster to a novel odorant compared to controls

• however, no difference in response is seen on the first exposure to a novel odorant

taste/olfaction

abnormal olfaction ( J:146630 )

• mice recover olfactory ability more quickly following exposure to dichlobenil compared to controls

neoplasm

neoplasm ( J:146630 , J:154673 )

N • in contrast to other conditional null Pten genotypes no tumors are found in mice up to 2 years of age (J:146630)

N (J:154673)

homeostasis/metabolism

abnormal response to CNS ischemic injury ( J:146630 )

• 7 days after induction of limited stroke in the sensorimotor cortex, mice have more neuroblasts in the peri-infarct cortex compared to controls

• however, there is no difference in the number of new cells present at 90 days after stroke induction

cellular

abnormal neuron differentiation ( J:146630 )

• cultured adult neural stem cells maintain their ability to differentiate into neurons for a longer time compared to wild-type cells

abnormal neuronal precursor proliferation ( J:146630 )

• in culture, neurospheres formed by adult neural stem cells are generally larger and the stem cells' capacity for self renewal is prolonged compared to wild-type cells

Genotype
MGI:4849441

cn98

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten⁺; Tg(Gfap-cre)77.6Mvs/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6NHsd

mortality/aging

premature death ( J:154673 )

• survival is on average 22 weeks

neoplasm

increased classified tumor incidence ( J:154673 )

• mutants develop multiple visible subcutaneous tumors with 100% penetrance, starting from 4 months of age

• majority of tumors are located on the back and sides

increased neurofibroma incidence ( J:154673 )

• each mutant has more than one lesion with features of human neurofibroma and malignant peripheral nerve sheath tumor

increased neurofibrosarcoma incidence ( J:154673 )

• progressive development of malignant peripheral nerve sheath tumors (MPNST) from neurofibroma, with 100% of mutants showing MPNST when followed for 7 months

• Pten loss of heterozygosity in mutants correlates with MPNST transformation from neurofibromas

nervous system

increased neurofibroma incidence ( J:154673 )

• each mutant has more than one lesion with features of human neurofibroma and malignant peripheral nerve sheath tumor

increased neurofibrosarcoma incidence ( J:154673 )

• progressive development of malignant peripheral nerve sheath tumors (MPNST) from neurofibroma, with 100% of mutants showing MPNST when followed for 7 months

• Pten loss of heterozygosity in mutants correlates with MPNST transformation from neurofibromas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant peripheral nerve sheath tumor		DOID:5940		J:154673
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:154673

Genotype
MGI:4943565

cn99

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Scgb1a1-cre)1Tauc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

respiratory system

respiratory system phenotype ( J:136369 )

N • numbers of bronchioalveolar stem cells in terminal bronchi are normal

Genotype
MGI:4836606

cn100

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

respiratory system

increased club cell number ( J:157922 )

• increase in the numbers of Clara cells in the lungs

Genotype
MGI:4849440

cn101

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Slc6a3^{tm1.1(cre)Bkmn}/Slc6a3⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

Altered dopamine neurons in the ventral midbrain of Pten^tm1Hwu/Pten^tm1Hwu Slc6a3^{tm1.1(cre)Bkmn}/Slc6a3⁺ mice

behavior/neurological

behavior/neurological phenotype ( J:153622 )

N • no difference in locomotor activity is seen compared to controls during exposure to a novel environment

abnormal behavioral response to xenobiotic ( J:153622 )

• mutants exhibit a significant reduction in ipsilateral rotational behavior in response to amphetamine administration after 6OHDA lesioning

nervous system

abnormal midbrain morphology ( J:153622 )

• neuronal hypertrophy in the ventral midbrain resulting in enlargement of the ventral midbrain area

• increase in the number of TH positive neurons in the substantia nigra compacta and ventral tegmental area of the adult ventral midbrain and an increase in neuronal soma size

abnormal substantia nigra pars compacta morphology ( J:153622 )

• increase in the number of TH positive neurons in the substantia nigra compacta

abnormal substantia nigra pars reticulata morphology ( J:153622 )

• increase in the number of dopaminergic neuron dendritic processes in the substantia nigra pars reticulata

abnormal striatum morphology ( J:153622 )

• modest but significant enlargement of the caudal striatum

abnormal dopaminergic neuron morphology ( J:153622 )

• increase in number of dopaminergic neurons and fibers in the ventral mesencephalon

• dopaminergic neurons in the ventral midbrain are larger in size and have an increase in the number of dendritic processes in the substantia nigra pars reticulata

neuron hypertrophy ( J:153622 )

• hypertrophy of dopamine neurons

abnormal nervous system physiology ( J:153622 )

• mutant dopamine neurons are protected from 6OHDA induced lesions, fiber loss, and axonal loss in the striatum compared to controls

homeostasis/metabolism

increased dopamine level ( J:153622 )

• increase in total dopamine tissue levels in the dorsal striatum and midbrain, however, no alterations in basal dopamine extracellular levels or evoked dopamine release in the dorsal striatum

Genotype
MGI:4882032

cn102

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Gdf9-icre)5092Coo/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

endocrine/exocrine glands

abnormal primordial ovarian follicle morphology ( J:151696 )

♀ • females exhibit prematurely activated primordial follicles (transient follicles with enlarged oocytes surrounded by flattened pre-granulosa cells) leading to complete depletion of follicles by 16 weeks of age

reproductive system

abnormal primordial ovarian follicle morphology ( J:151696 )

♀ • females exhibit prematurely activated primordial follicles (transient follicles with enlarged oocytes surrounded by flattened pre-granulosa cells) leading to complete depletion of follicles by 16 weeks of age

Genotype
MGI:4943568

cn103

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Scgb1a1-cre)1Tauc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

respiratory system

abnormal bronchiole morphology ( J:136369 )

• bronchioles exhibit clusters of CCSP+SPC+ cells (indicators of BASCs) as early as 4 weeks of age that are not seen in controls

abnormal bronchus morphology ( J:136369 )

• mutants exhibit expansion of bronchioalveolar stem cells (BASCs) in terminal bronchi

• small bronchi exhibit clusters of CCSP+SPC+ cells (indicators of BASCs) as early as 4 weeks of age that are not seen in controls

Genotype
MGI:5008585

cn104

• Allelic Composition: Gt(ROSA)26Sor^{tm9(cre/ESR1)Arte}/Gt(ROSA)26Sor⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

premature death ( J:170965 )

• tamoxifen-treated mice survive 65 days compared with Pdk1^tm1Dral Gt(ROSA)26Sor^{tm9(cre/ESR1)Arte} mice that survive 57

immune system

enlarged spleen ( J:170965 )

• in tamoxifen-treated mice

increased spleen weight ( J:170965 )

• in tamoxifen-treated mice

enlarged lymph nodes ( J:170965 )

• in tamoxifen-treated mice

neoplasm

increased acute lymphoblastic leukemia incidence ( J:170965 )

• in tamoxifen-treated mice

behavior/neurological

hunched posture ( J:170965 )

• in tamoxifen-treated mice

hematopoietic system

enlarged spleen ( J:170965 )

• in tamoxifen-treated mice

increased spleen weight ( J:170965 )

• in tamoxifen-treated mice

growth/size/body

enlarged spleen ( J:170965 )

• in tamoxifen-treated mice

increased spleen weight ( J:170965 )

• in tamoxifen-treated mice

Genotype
MGI:5008587

cn105

• Allelic Composition: Gt(ROSA)26Sor^{tm1(H1/tetO-RNAi:Pdpk1)Mrl}/Gt(ROSA)26Sor^{tm9(cre/ESR1)Arte}; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

premature death ( J:170965 )

• tamoxifen-treated mice survive 57 days unlike control mice

immune system

enlarged spleen ( J:170965 )

• in tamoxifen-treated mice

increased spleen weight ( J:170965 )

• in tamoxifen-treated mice

increased memory B cell number ( J:170965 )

• in tamoxifen-treated mice

decreased B cell number ( J:170965 )

• in tamoxifen-treated mice

enlarged lymph nodes ( J:170965 )

• in tamoxifen-treated mice

neoplasm

increased acute lymphoblastic leukemia incidence ( J:170965 )

• tamoxifen-treated mice develop T cell acute lymphoblastic leukemia unlike control mice

behavior/neurological

hunched posture ( J:170965 )

• in tamoxifen-treated mice

growth/size/body

weight loss ( J:170965 )

• in tamoxifen-treated mice

enlarged spleen ( J:170965 )

• in tamoxifen-treated mice

increased spleen weight ( J:170965 )

• in tamoxifen-treated mice

integument

disheveled coat ( J:170965 )

• scruffy coat in tamoxifen-treated mice

hematopoietic system

enlarged spleen ( J:170965 )

• in tamoxifen-treated mice

increased spleen weight ( J:170965 )

• in tamoxifen-treated mice

increased memory B cell number ( J:170965 )

• in tamoxifen-treated mice

decreased B cell number ( J:170965 )

• in tamoxifen-treated mice

Genotype
MGI:5688871

cn106

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(CD2-icre)4Kio/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca

hematopoietic system

enlarged thymus ( J:216983 )

• at 6-8 weeks of age

endocrine/exocrine glands

enlarged thymus ( J:216983 )

• at 6-8 weeks of age

immune system

enlarged thymus ( J:216983 )

• at 6-8 weeks of age

Genotype
MGI:5688869

cn107

• Allelic Composition: Pkn3^tm1.1Mrl/Pkn3^tm1.1Mrl; Pten^tm1Hwu/Pten^tm1Hwu; Tg(CD2-icre)4Kio/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:216983 )

N • thymus weight is similar to controls at 6-8 weeks of age unlike in mutant mice wild-type for Pkn3

Genotype
MGI:5007630

cn108

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J * CBA

hematopoietic system

thrombocytosis ( J:165893 )

• mutants injected with poly(I:C) to induce cre expression, exhibit 25% more platelets in the blood than controls

abnormal platelet activation ( J:165893 )

• collagen-induced platelet activation is enhanced in mutants injected with poly(I:C) to induce cre expression

increased platelet aggregation ( J:165893 )

• platelets of mutants injected with poly(I:C) to induce cre expression are induced to aggregate by a much lower level of collagen than is required to induce the same response by wild-type platelets

homeostasis/metabolism

abnormal platelet activation ( J:165893 )

• collagen-induced platelet activation is enhanced in mutants injected with poly(I:C) to induce cre expression

increased platelet aggregation ( J:165893 )

• platelets of mutants injected with poly(I:C) to induce cre expression are induced to aggregate by a much lower level of collagen than is required to induce the same response by wild-type platelets

decreased bleeding time ( J:165893 )

• mutants injected with poly(I:C) to induce cre expression have an average bleeding time that is shorter than in controls

Genotype
MGI:6198766

cn109

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(CAG-MYC,-GFP*)#Rugg/0; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J * DBA/2

mortality/aging

premature death ( J:261540 )

♂ • mice show decreased overall survival, with a mean life span of 75 weeks

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:261540 )

♂ • mice develop prostatic adenocarcinoma by 10 weeks of age

♂ • mice with developed tumors treated with a small-molecule inhibitor of P-eIF2alpha activity, ISRIB, show tumor regression within 3 weeks of treatment, with no signs of toxicity

increased prostate intraepithelial neoplasia incidence ( J:261540 )

♂ • mice show enlargement of prostate growth by 6 weeks of age and accelerated development of high-grade prostatic intraepithelial neoplasia compared to single conditional Pten^tm1Hwu mutants

neoplasm

increased prostate gland adenocarcinoma incidence ( J:261540 )

♂ • mice develop prostatic adenocarcinoma by 10 weeks of age

♂ • mice with developed tumors treated with a small-molecule inhibitor of P-eIF2alpha activity, ISRIB, show tumor regression within 3 weeks of treatment, with no signs of toxicity

increased prostate intraepithelial neoplasia incidence ( J:261540 )

♂ • mice show enlargement of prostate growth by 6 weeks of age and accelerated development of high-grade prostatic intraepithelial neoplasia compared to single conditional Pten^tm1Hwu mutants

reproductive system

increased prostate gland adenocarcinoma incidence ( J:261540 )

♂ • mice develop prostatic adenocarcinoma by 10 weeks of age

♂ • mice with developed tumors treated with a small-molecule inhibitor of P-eIF2alpha activity, ISRIB, show tumor regression within 3 weeks of treatment, with no signs of toxicity

increased prostate intraepithelial neoplasia incidence ( J:261540 )

♂ • mice show enlargement of prostate growth by 6 weeks of age and accelerated development of high-grade prostatic intraepithelial neoplasia compared to single conditional Pten^tm1Hwu mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:261540

Genotype
MGI:5529025

cn110

• Allelic Composition: Mirc14^tm1.1Flv/Mirc14^tm1.1Flv; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6N * DBA/2 * SJL

immune system

immune system phenotype ( J:203157 )

N • NKT cell development is rescued

Genotype
MGI:5013485

cn111

• Allelic Composition: Lepr^db/Lepr^db; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BLKS/J * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:170206 )

N • mutants are protected from developing diabetes, and despite severe insulin resistance, mutants remain euglycemic and show normal glucose tolerance

increased insulin secretion ( J:170206 )

• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Lepr^db mice

insulin resistance ( J:170206 )

• mutants exhibit a similar degree of insulin resistance as single Lepr^db mice

growth/size/body

increased body weight ( J:170206 )

• mutants exhibit a similar degree of weight gain as single homozygous Lepr^db mice

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:170206 )

• islets show similar degrees of hypertrophy and proliferation as those in single homozygous Lepr^db mice and do not show a further increase in beta-cell mass compared to the single Lepr^db mice

increased insulin secretion ( J:170206 )

• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Lepr^db mice

Genotype
MGI:4836620

cn112

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

digestive/alimentary system

intestine polyps ( J:118329 )

• mice develop multiple polyps in the small intestine one month after completion of pIpC injection to induce Cre expression

• polyps show a large excess of crypt-like units at their base and aberrant positioning of crypts along the edges of villi

• overgrowth and insertions of stromal cells from the base of the polypoid mass are seen in the small intestine one month after completion of pIpC injection to induce Cre expression

• intestinal stem cells exhibit increased proliferation due to Akt activation and nuclear localization of beta-catenin resulting in an increase of intestinal stem cells in the crypts

• these excess stem cells initiate de novo crypt formation and crypt fission at a higher rate than in controls

neoplasm

increased acute lymphoblastic leukemia incidence ( J:169097 )

• mice injected with pIpC to induce Pten deletion, develop myeloproliferative disease and T-cell acute lymphoblastic leukemia

immune system

enlarged thymus ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged thymus

enlarged spleen ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged spleen

mortality/aging

premature death ( J:169097 )

• mean survival time of mice injected with pIpC to induce Pten deletion is 35 days

hematopoietic system

enlarged thymus ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged thymus

enlarged spleen ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged spleen

endocrine/exocrine glands

enlarged thymus ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged thymus

growth/size/body

enlarged spleen ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged spleen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute lymphoblastic leukemia		DOID:9952	OMIM:247640 OMIM:613065	J:169097
Cowden syndrome		DOID:6457	OMIM:PS158350	J:118329

Genotype
MGI:4836238

cn113

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pdx1-cre/Esr1*)35.10Dam/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:102226 )

• mice injected with tamoxifen at 2-3 weeks of age, exhibit islet hyperplasia but no ductal abnormalities or increase in DBA staining

Genotype
MGI:4943267

cn114

• Allelic Composition: Apc^tm1Tno/Apc^tm1Tno; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Cyp1a1-cre/ERT)1Dwi/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

renal/urinary system

abnormal urinary bladder urothelium morphology ( J:164579 )

• mice develop hyperplastic lesions in the bladder unlike wild-type mice that are larger than in Apc^tm1Tno/Apc^tm1Tno Tg(Cyp1a1-cre/ERT)1Dwi mice

Genotype
MGI:4836237

cn115

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

mortality/aging

premature death ( J:102226 )

• at about 2-3 months of age, mutants show signs of illness, with wasting, respiratory distress and frequently die before 6 months of age

digestive/alimentary system

abnormal exocrine pancreas morphology ( J:102226 )

• mice exhibit ductal metaplasia that appears to result from expansion of centroacinar cells rather than transdifferentiation of acinar cells

abnormal pancreatic acinus morphology ( J:102226 )

• mutants exhibit progressive replacement of the acinar pancreas with highly proliferative ductual structures that contain abundant mucins and markers of pancreatic progenitor cells

• preweaned mutants show a 4-fold increase in BrdU incorporation in the acinar pancreas, particularly in the centroacinar position and epithelial cells within large ducts, indicating increased proliferation

abnormal centroacinar cell of Langerhans morphology ( J:102226 )

• increase in centroacinar cells in the pancreas that are present in groups of 4-8 cells compared to single or doublet centroacinar cells in wild-type

abnormal pancreatic acinar cell morphology ( J:102226 )

• increase in centroacinar cell proliferation and an increase in apoptosis of acinar cells in transitional areas

increased pancreatic acinar cell number ( J:102226 )

endocrine/exocrine glands

abnormal exocrine pancreas morphology ( J:102226 )

• mice exhibit ductal metaplasia that appears to result from expansion of centroacinar cells rather than transdifferentiation of acinar cells

abnormal pancreatic acinus morphology ( J:102226 )

• mutants exhibit progressive replacement of the acinar pancreas with highly proliferative ductual structures that contain abundant mucins and markers of pancreatic progenitor cells

• preweaned mutants show a 4-fold increase in BrdU incorporation in the acinar pancreas, particularly in the centroacinar position and epithelial cells within large ducts, indicating increased proliferation

abnormal centroacinar cell of Langerhans morphology ( J:102226 )

• increase in centroacinar cells in the pancreas that are present in groups of 4-8 cells compared to single or doublet centroacinar cells in wild-type

abnormal pancreatic acinar cell morphology ( J:102226 )

• increase in centroacinar cell proliferation and an increase in apoptosis of acinar cells in transitional areas

increased pancreatic acinar cell number ( J:102226 )

enlarged pancreatic islets ( J:102226 )

• newborns exhibit enlarged and irregularly shaped islets

pancreatic islet hyperplasia ( J:102226 )

increased pancreatic ductal adenocarcinoma incidence ( J:102226 )

• one 11-week old mutant developed papillary ductal adenocarcinoma while a 13-month old mutant developed a pancreatic ductal adenocarcinoma that invaded into the duodenum and exhibited a desmosplastic stroma

increased pancreatic intraepithelial neoplasia incidence ( J:102226 )

• mice exhibit widespread ductal metaplasia with increased mucin production and develop PanIN lesions and malignant transformation with low frequency

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:102226 )

N • fed and fasting blood glucose levels and glucose tolerance are normal

neoplasm

increased pancreatic intraepithelial neoplasia incidence ( J:102226 )

• mice exhibit widespread ductal metaplasia with increased mucin production and develop PanIN lesions and malignant transformation with low frequency

increased malignant tumor incidence ( J:102226 )

• 2 of 14 mice develop ductal malignancy in the pancreas

increased pancreatic ductal adenocarcinoma incidence ( J:102226 )

• one 11-week old mutant developed papillary ductal adenocarcinoma while a 13-month old mutant developed a pancreatic ductal adenocarcinoma that invaded into the duodenum and exhibited a desmosplastic stroma

Genotype
MGI:5688868

cn116

• Allelic Composition: Pkn3^tm1.1Mrl/Pkn3⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA/J

mortality/aging

premature death ( J:216983 )

• lifespan after pIpC treatment is shorter than in controls and in mutant nice with no wild-type Pkn3 alleles

neoplasm

increased hemolymphoid system tumor incidence ( J:216983 )

• develop myeloproliferative neoplasms in the spleen 2 weeks after pIpC treatment

increased acute lymphoblastic leukemia incidence ( J:216983 )

• all eventually develop T cell acute lymphoblastic leukemia after pIpC treatment at 6 weeks of age

hematopoietic system

enlarged thymus ( J:216983 )

• at 2 weeks after pIpC treatment

enlarged spleen ( J:216983 )

• at 2 weeks after pIpC treatment

extramedullary hematopoiesis ( J:216983 )

• increase in the number of hematopoietic stem cells in the spleen 2 weeks after pIpC treatment

endocrine/exocrine glands

enlarged thymus ( J:216983 )

• at 2 weeks after pIpC treatment

immune system

enlarged thymus ( J:216983 )

• at 2 weeks after pIpC treatment

enlarged spleen ( J:216983 )

• at 2 weeks after pIpC treatment

growth/size/body

enlarged spleen ( J:216983 )

• at 2 weeks after pIpC treatment

Genotype
MGI:5688867

cn117

• Allelic Composition: Pkn3^tm1.1Mrl/Pkn3^tm1.1Mrl; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA/J

mortality/aging

premature death ( J:216983 )

• lifespan after pIpC treatment is shorter than in controls but longer than in mutant nice with one wild-type Pkn3 allele

neoplasm

increased hemolymphoid system tumor incidence ( J:216983 )

• develop myeloproliferative neoplasms in the spleen 2 weeks after pIpC treatment

increased acute lymphoblastic leukemia incidence ( J:216983 )

• all eventually develop T cell acute lymphoblastic leukemia after pIpC treatment at 6 weeks of age

hematopoietic system

enlarged thymus ( J:216983 )

• at 2 weeks after pIpC treatment

• thymus is smaller than in mutant mice with one wild-type Pkn3 allele

enlarged spleen ( J:216983 )

• at 2 weeks after pIpC treatment

extramedullary hematopoiesis ( J:216983 )

• increase in the number of hematopoietic stem cells in the spleen 2 weeks after pIpC treatment

endocrine/exocrine glands

enlarged thymus ( J:216983 )

• at 2 weeks after pIpC treatment

• thymus is smaller than in mutant mice with one wild-type Pkn3 allele

immune system

enlarged thymus ( J:216983 )

• at 2 weeks after pIpC treatment

• thymus is smaller than in mutant mice with one wild-type Pkn3 allele

enlarged spleen ( J:216983 )

• at 2 weeks after pIpC treatment

growth/size/body

enlarged spleen ( J:216983 )

• at 2 weeks after pIpC treatment

Genotype
MGI:4829790

cn118

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA

liver/biliary system

increased hepatocyte apoptosis ( J:218587 )

♂ • progressive hepatocyte cell death as mice progress from steatosis to premalignancy, with massive hepatocyte death by 9 months of age

increased hepatocyte proliferation ( J:218587 )

♂ • at 12 months of age, livers show increased cell proliferation

increased cholangiocarcinoma incidence ( J:218587 )

♂ • tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma

abnormal liver morphology ( J:218587 )

♂ • progressive and chronic liver injury that begins before proliferation of hepatic progenitors

♂ • accumulation of hepatic progenitor cells in the periductal region of livers from 9-12 months of age

♂ • liver shows multiple layers of progenitor cells surrounding a single layer of ductal cells which show high mitotic activity after 9 months of age

enlarged liver ( J:88441 , J:171445 )

• mutants exhibit enlarged, whitish livers containing large fat vacuoles by 12 weeks of age (J:171445)

• mutants treated with rapamycin show reduced hepatocyte cell size, thus reducing the liver:body weight ratio (J:171445)

increased liver weight ( J:88441 , J:160759 )

increased liver glycogen level ( J:88441 )

• increase in glycogen storage in the liver

increased liver triglyceride level ( J:88441 , J:160759 )

• 3-fold increase in triglyceride content in the liver (J:88441)

• however, normal levels of plasma triglycerides (J:88441)

• 2-4-fold increase of triglyceride content in the liver of 1 and 3 month old mutants, respectively (J:160759)

hepatic steatosis ( J:88441 , J:160759 , J:218587 )

• progressive development of fatty liver (J:88441)

♂ (J:218587)

macrovesicular hepatic steatosis ( J:171445 )

• mutants exhibit enlarged, whitish livers containing large fat vacuoles by 12 weeks of age

• mutants treated with rapamycin exhibit no differences in steatosis compared to vehicle-treated mutants

increased liver tumor incidence ( J:218587 )

♂ • mice develop liver tumors starting at approximately 8-9 months of age

♂ • 50% of mice develop tumors between 9 and 12 months of age and 100% develop tumors by 12 months of age

♂ • tumors show mixed cell characteristics, with tumors composed of colangiocytes, hepatocytes, and bi-lineage cells

increased hepatocellular carcinoma incidence ( J:218587 )

♂ • tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma

pale liver ( J:88441 )

adipose tissue

decreased total body fat amount ( J:88441 )

• 50% reduction in total body fat content

homeostasis/metabolism

decreased circulating glucose level ( J:88441 )

• decrease in fasting glucose levels at 1 and 3 months of age, however at 6 months of age, when severe steatosis is seen, the fasting glucose level is similar to wild-type

decreased circulating insulin level ( J:88441 )

• decrease in fasting plasma insulin levels at 3 and 6 months of age

decreased circulating leptin level ( J:88441 )

• decrease in serum leptin levels at one month of age

• however eating behavior is normal

increased circulating alanine transaminase level ( J:218587 )

♂ • serum alanine aminotransferase levels increase progressively, reaching 5-fold higher levels at 12 months of age

improved glucose tolerance ( J:88441 )

• increase in glucose clearance during an intraperitoneal glucose load

increased liver glycogen level ( J:88441 )

• increase in glycogen storage in the liver

increased insulin sensitivity ( J:88441 )

• increase in insulin sensitivity in the liver

abnormal fatty acids level ( J:88441 )

• hepatocyte fatty acid uptake by passive diffusion is increased by 20% compared to controls, however active transportation of fatty acid is not changed and thus total fatty acid uptake is not significantly altered

• rate of fatty acid synthesis is 2.5-fold higher in mutant livers than in controls

decreased circulating free fatty acids level ( J:88441 )

• 30% decrease in circulating free fatty acids

increased liver triglyceride level ( J:88441 , J:160759 )

• 3-fold increase in triglyceride content in the liver (J:88441)

• however, normal levels of plasma triglycerides (J:88441)

• 2-4-fold increase of triglyceride content in the liver of 1 and 3 month old mutants, respectively (J:160759)

impaired lipolysis ( J:88441 )

• decrease in lipolysis rate

growth/size/body

enlarged liver ( J:88441 , J:171445 )

• mutants exhibit enlarged, whitish livers containing large fat vacuoles by 12 weeks of age (J:171445)

• mutants treated with rapamycin show reduced hepatocyte cell size, thus reducing the liver:body weight ratio (J:171445)

increased liver weight ( J:88441 , J:160759 )

cellular

increased hepatocyte apoptosis ( J:218587 )

♂ • progressive hepatocyte cell death as mice progress from steatosis to premalignancy, with massive hepatocyte death by 9 months of age

increased hepatocyte proliferation ( J:218587 )

♂ • at 12 months of age, livers show increased cell proliferation

oxidative stress ( J:218587 )

♂ • marker analysis indicates oxidative stress in the liver

neoplasm

increased cholangiocarcinoma incidence ( J:218587 )

♂ • tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma

increased liver tumor incidence ( J:218587 )

♂ • mice develop liver tumors starting at approximately 8-9 months of age

♂ • 50% of mice develop tumors between 9 and 12 months of age and 100% develop tumors by 12 months of age

♂ • tumors show mixed cell characteristics, with tumors composed of colangiocytes, hepatocytes, and bi-lineage cells

increased hepatocellular carcinoma incidence ( J:218587 )

♂ • tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma

endocrine/exocrine glands

increased cholangiocarcinoma incidence ( J:218587 )

♂ • tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:218587
steatotic liver disease		DOID:9452	OMIM:228100	J:216841

Genotype
MGI:4839070

cn119

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA

cellular

decreased cellular sensitivity to oxidative stress ( J:106937 )

• islets are protected from oxidative stress

increased pancreatic beta cell proliferation ( J:106937 )

• increase in beta-cell proliferation at E17.5

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:170206 )

• increase in beta cell size

• beta-cells maintain intact response to DNA-damaging stimuli unlike controls

increased pancreatic beta cell mass ( J:170206 )

• increase in beta cell mass, due to an increase in proliferation and in beta cell size

• however, mutants do not exhibit any further increase in beta-cell mass on a high-fat diet

increased pancreatic beta cell number ( J:106937 )

• number of insulin-producing cells is increased in islets

increased pancreatic islet number ( J:106937 )

• 1.5-fold increase in islet numbers

enlarged pancreatic islets ( J:106937 )

• 2-fold increase in islet size

abnormal pancreas physiology ( J:106937 )

• decrease in apoptotic rate during pancreas remodeling at P17

• however, pancreas exhibits normal islet functions

increased pancreatic beta cell proliferation ( J:106937 )

• increase in beta-cell proliferation at E17.5

increased insulin secretion ( J:170206 )

• after high-fat diet feeding, mutants maintain robust insulin secretion in response to glucose compared to controls which show attenuation of insulin secretion, indicating that mutant islets are protected against high-fat diet-induced beta-cell dysfunction

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:170206 )

N • despite weight gain, mutants are protected from high-fat diet-induced diabetes, remaining euglycemic and showing improved glucose tolerance than controls on a high-fat diet

increased insulin secretion ( J:170206 )

• after high-fat diet feeding, mutants maintain robust insulin secretion in response to glucose compared to controls which show attenuation of insulin secretion, indicating that mutant islets are protected against high-fat diet-induced beta-cell dysfunction

hypoglycemia ( J:106937 )

• hypoglycemia, however mice respond normally to a glucose challenge

improved glucose tolerance ( J:170206 )

• mutants are protected from high-fat diet-induced diabetes, remaining euglycemic and showing improved glucose tolerance than controls on a high-fat diet

increased insulin sensitivity ( J:170206 )

• increase in peripheral insulin sensitivity

decreased susceptibility to injury ( J:106937 )

• mice are protected from STZ-induced beta-cell injury and diabetes

growth/size/body

increased body weight ( J:170206 )

Genotype
MGI:4358249

cn120

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

mortality/aging

mortality/aging ( J:212219 )

♂N • mice survive at least 1 year

reproductive system

enlarged prostate gland anterior lobe ( J:170965 )

♂

increased prostate gland weight ( J:170965 )

♂

prostate gland hyperplasia ( J:170965 )

♂

increased prostate gland tumor incidence ( J:170965 , J:172730 , J:268934 )

♂ • mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1^tm1Dral homozygotes (J:170965)

♂ • mutants develop castrate-resistant prostate cancer (J:172730)

♂ • mice develop intracystic prostatic carcinomas between 4 and 10 months of age (J:268934)

increased prostate gland adenocarcinoma incidence ( J:184935 , J:212219 , J:268934 )

♂ • mice predominately develop adenocarcinoma localized to the dorsolateral lobes of the prostate (J:184935)

♂ • localized lesions that slowly progress to prostate adenocarcinomas (J:212219)

♂ • 4 of 8 mice develop prostatic adenocarcinoma and 3 of 8 mice exhibit invasive carcinomas after 10 months (J:268934)

increased prostate intraepithelial neoplasia incidence ( J:131932 , J:212219 , J:268934 )

♂ • in lesions, basal cells are not disorganized in contrast to Tg(Pbsn-ERG*)1Vv mice at 7 weeks (J:131932)

♂ • localized lesions that slowly progress to prostate adenocarcinomas (J:212219)

♂ • 4 of 4 mice develop low grade pancreatic intraepithelial neoplasia (PIN) and 2 of 4 mice show multifocal high grade PIN before 4 months of age (J:268934)

♂ • 6 of 6 mice exhibit multifocal high grade PIN at 4-10 months of age (J:268934)

neoplasm

increased prostate gland tumor incidence ( J:170965 , J:172730 , J:268934 )

♂ • mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1^tm1Dral homozygotes (J:170965)

♂ • mutants develop castrate-resistant prostate cancer (J:172730)

♂ • mice develop intracystic prostatic carcinomas between 4 and 10 months of age (J:268934)

increased prostate gland adenocarcinoma incidence ( J:184935 , J:212219 , J:268934 )

♂ • mice predominately develop adenocarcinoma localized to the dorsolateral lobes of the prostate (J:184935)

♂ • localized lesions that slowly progress to prostate adenocarcinomas (J:212219)

♂ • 4 of 8 mice develop prostatic adenocarcinoma and 3 of 8 mice exhibit invasive carcinomas after 10 months (J:268934)

increased prostate intraepithelial neoplasia incidence ( J:131932 , J:212219 , J:268934 )

♂ • in lesions, basal cells are not disorganized in contrast to Tg(Pbsn-ERG*)1Vv mice at 7 weeks (J:131932)

♂ • localized lesions that slowly progress to prostate adenocarcinomas (J:212219)

♂ • 4 of 4 mice develop low grade pancreatic intraepithelial neoplasia (PIN) and 2 of 4 mice show multifocal high grade PIN before 4 months of age (J:268934)

♂ • 6 of 6 mice exhibit multifocal high grade PIN at 4-10 months of age (J:268934)

increased metastatic potential ( J:268934 )

♂ • prostate cancer metastasis after 10 months of age, with 12.5% of mice showing metastatic lesions to lungs and lymph nodes

increased carcinoma incidence ( J:268934 )

♂ • 2 of 6 mice develop intracystic prostatic carcinomas between 4 and 10 months of age

♂ • 6 of 8 mice show intracystic prostatic carcinoma after 10 months of age

endocrine/exocrine glands

enlarged prostate gland anterior lobe ( J:170965 )

♂

increased prostate gland weight ( J:170965 )

♂

prostate gland hyperplasia ( J:170965 )

♂

increased prostate gland tumor incidence ( J:170965 , J:172730 , J:268934 )

♂ • mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1^tm1Dral homozygotes (J:170965)

♂ • mutants develop castrate-resistant prostate cancer (J:172730)

♂ • mice develop intracystic prostatic carcinomas between 4 and 10 months of age (J:268934)

increased prostate gland adenocarcinoma incidence ( J:184935 , J:212219 , J:268934 )

♂ • mice predominately develop adenocarcinoma localized to the dorsolateral lobes of the prostate (J:184935)

♂ • localized lesions that slowly progress to prostate adenocarcinomas (J:212219)

♂ • 4 of 8 mice develop prostatic adenocarcinoma and 3 of 8 mice exhibit invasive carcinomas after 10 months (J:268934)

increased prostate intraepithelial neoplasia incidence ( J:131932 , J:212219 , J:268934 )

♂ • in lesions, basal cells are not disorganized in contrast to Tg(Pbsn-ERG*)1Vv mice at 7 weeks (J:131932)

♂ • localized lesions that slowly progress to prostate adenocarcinomas (J:212219)

♂ • 4 of 4 mice develop low grade pancreatic intraepithelial neoplasia (PIN) and 2 of 4 mice show multifocal high grade PIN before 4 months of age (J:268934)

♂ • 6 of 6 mice exhibit multifocal high grade PIN at 4-10 months of age (J:268934)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:172730 , J:184935

Genotype
MGI:5008589

cn121

• Allelic Composition: Gt(ROSA)26Sor^{tm2(H1/tetO-RNAi:Pdpk1)Mrl}/Gt(ROSA)26Sor⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

reproductive system

enlarged prostate gland anterior lobe ( J:170965 )

♂ • in doxycycline-treated mice

increased prostate gland weight ( J:170965 )

♂ • in doxycycline-treated mice

prostate gland hyperplasia ( J:170965 )

♂ • in doxycycline-treated mice

increased prostate gland tumor incidence ( J:170965 )

♂ • doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1^tm1Dral homozygotes

neoplasm

increased prostate gland tumor incidence ( J:170965 )

♂ • doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1^tm1Dral homozygotes

endocrine/exocrine glands

enlarged prostate gland anterior lobe ( J:170965 )

♂ • in doxycycline-treated mice

increased prostate gland weight ( J:170965 )

♂ • in doxycycline-treated mice

prostate gland hyperplasia ( J:170965 )

♂ • in doxycycline-treated mice

increased prostate gland tumor incidence ( J:170965 )

♂ • doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1^tm1Dral homozygotes

Genotype
MGI:5008586

cn122

• Allelic Composition: Gt(ROSA)26Sor^{tm1(H1/tetO-RNAi:Pdpk1)Mrl}/Gt(ROSA)26Sor⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

reproductive system

enlarged prostate gland anterior lobe ( J:170965 )

♂ • in doxycycline-treated mice

increased prostate gland weight ( J:170965 )

♂ • in doxycycline-treated mice

prostate gland hyperplasia ( J:170965 )

♂ • in doxycycline-treated mice

increased prostate gland tumor incidence ( J:170965 )

♂ • doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdk1^tm1Dral homozygotes

abnormal prostate gland physiology ( J:170965 )

♂ • doxycycline-treated mice exhibit increased proliferation in the prostate gland compared to in Pdk1^tm1Dral homozygotes

neoplasm

increased prostate gland tumor incidence ( J:170965 )

♂ • doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdk1^tm1Dral homozygotes

endocrine/exocrine glands

enlarged prostate gland anterior lobe ( J:170965 )

♂ • in doxycycline-treated mice

increased prostate gland weight ( J:170965 )

♂ • in doxycycline-treated mice

prostate gland hyperplasia ( J:170965 )

♂ • in doxycycline-treated mice

increased prostate gland tumor incidence ( J:170965 )

♂ • doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdk1^tm1Dral homozygotes

abnormal prostate gland physiology ( J:170965 )

♂ • doxycycline-treated mice exhibit increased proliferation in the prostate gland compared to in Pdk1^tm1Dral homozygotes

Genotype
MGI:5578649

cn123

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tmprss2^{tm2.1(ETV1)Sho}/Tmprss2^{tm2.1(ETV1)Sho}; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

mortality/aging

premature death ( J:212219 )

♂ • most mice die before 1 year of age

reproductive system

increased prostate gland adenocarcinoma incidence ( J:212219 )

♂ • invasive with metastasis into the prostate stroma and urogenital area

prostate gland cyst ( J:212219 )

♂ • large

neoplasm

increased prostate gland adenocarcinoma incidence ( J:212219 )

♂ • invasive with metastasis into the prostate stroma and urogenital area

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:212219 )

♂ • invasive with metastasis into the prostate stroma and urogenital area

prostate gland cyst ( J:212219 )

♂ • large

growth/size/body

prostate gland cyst ( J:212219 )

♂ • large

Genotype
MGI:5578652

cn124

• Allelic Composition: Erg^tm1.1Sho/Erg^tm1.1Sho; Pten^tm1Hwu/Pten^tm1Hwu; Tmprss2^tm3Sho/Tmprss2^tm3Sho; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:212219 )

♂ • regions of invasive prostate adenocarcinoma in mice over 1 year of age

mortality/aging

mortality/aging ( J:212219 )

♂N • mice survive at least 1 year

neoplasm

increased prostate gland adenocarcinoma incidence ( J:212219 )

♂ • regions of invasive prostate adenocarcinoma in mice over 1 year of age

reproductive system

increased prostate gland adenocarcinoma incidence ( J:212219 )

♂ • regions of invasive prostate adenocarcinoma in mice over 1 year of age

Genotype
MGI:5705321

cn125

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

neoplasm

increased prostate gland adenocarcinoma incidence ( J:184935 )

♂ • mice develop invasive carcinoma in both the dorsolateral and anterior lobes of the prostate as early as 4 weeks with poorly differentiated carcinoma by 10 weeks

♂ • marker analysis indicates that prostatic epithelial cells undergo epithelial-to-mesenchymal transition and that tumors exhibit a human metastatic prostate cancer signature

increased metastatic potential ( J:184935 )

♂ • mice develop macrometastatic lesions in the lung and liver with 100% penetrance

mortality/aging

premature death ( J:184935 )

♂ • early lethality, with mice dying between around 10 and 30 weeks of age

endocrine/exocrine glands

abnormal prostate gland morphology ( J:184935 )

♂ • prostates show an expansion of the leukemia stem cell (LSC)^high subpopulation of stem/progenitor cells

♂ • both the LSC^high (basal cell population) and LSC^low (luminal cell population) subpopulations show enhanced sphere-forming in vitro

increased prostate gland adenocarcinoma incidence ( J:184935 )

♂ • mice develop invasive carcinoma in both the dorsolateral and anterior lobes of the prostate as early as 4 weeks with poorly differentiated carcinoma by 10 weeks

♂ • marker analysis indicates that prostatic epithelial cells undergo epithelial-to-mesenchymal transition and that tumors exhibit a human metastatic prostate cancer signature

reproductive system

abnormal prostate gland morphology ( J:184935 )

♂ • prostates show an expansion of the leukemia stem cell (LSC)^high subpopulation of stem/progenitor cells

♂ • both the LSC^high (basal cell population) and LSC^low (luminal cell population) subpopulations show enhanced sphere-forming in vitro

increased prostate gland adenocarcinoma incidence ( J:184935 )

♂ • mice develop invasive carcinoma in both the dorsolateral and anterior lobes of the prostate as early as 4 weeks with poorly differentiated carcinoma by 10 weeks

♂ • marker analysis indicates that prostatic epithelial cells undergo epithelial-to-mesenchymal transition and that tumors exhibit a human metastatic prostate cancer signature

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:184935

Genotype
MGI:5705328

cn126

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten⁺; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

mortality/aging

premature death ( J:184935 )

♂ • lethality around 40 weeks of age

neoplasm

increased prostate gland adenocarcinoma incidence ( J:184935 )

♂ • mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 weeks

increased metastatic potential ( J:184935 )

♂ • mice develop macrometastatic lesions in the lung and liver with 100% penetrance

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:184935 )

♂ • mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 weeks

reproductive system

increased prostate gland adenocarcinoma incidence ( J:184935 )

♂ • mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:184935

Genotype
MGI:4837112

cn127

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Plp1-cre/ERT2)1Ueli/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

nervous system

abnormal brain white matter morphology ( J:161841 )

• mice treated with tamoxifen to induce cre-recombination exhibit an increase in white matter volume

abnormal corpus callosum morphology ( J:161841 )

• many axons in the corpus callosum are hypermyelinated when mice are treated with tamoxifen to induce cre-recombination

abnormal myelin sheath morphology ( J:161841 )

• increase in myelin sheath thickness

• outfoldings of the myelin sheaths in CNS and PNS are observed

abnormal optic nerve morphology ( J:161841 )

• axons in the optic nerve are hypermyelinated when mice are treated with tamoxifen to induce cre-recombination

hypermyelination ( J:161841 )

• many axons in the corpus callosum and optic nerve are hypermyelinated when mice are treated with tamoxifen to induce cre-recombination

• normally nonmyelinated C-fiber axons are spirally enwrapped by Remak Schwann cells are seen in mice treated with tamoxifen to induce cre-recombination

vision/eye

abnormal optic nerve morphology ( J:161841 )

• axons in the optic nerve are hypermyelinated when mice are treated with tamoxifen to induce cre-recombination

Genotype
MGI:6378626

cn128

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Ptpn1^tm1Bpk/Ptpn1^tm1Bpk; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:231906 )

♂ • one mouse at 6 weeks of age shows a microinvasive adenocarcinoma

♂ • mice fed a high-fat diet upon weaning show an increase in the penetrance and number of microinvasive foci of microinvasive adenocarcinoma

increased prostate intraepithelial neoplasia incidence ( J:231906 )

♂ • mice show a similar number of prostate ductules affected by intraepithelial neoplasia (mPIN) as single Pten^tm1Hwu conditional mice

neoplasm

increased prostate gland adenocarcinoma incidence ( J:231906 )

♂ • one mouse at 6 weeks of age shows a microinvasive adenocarcinoma

♂ • mice fed a high-fat diet upon weaning show an increase in the penetrance and number of microinvasive foci of microinvasive adenocarcinoma

increased prostate intraepithelial neoplasia incidence ( J:231906 )

♂ • mice show a similar number of prostate ductules affected by intraepithelial neoplasia (mPIN) as single Pten^tm1Hwu conditional mice

reproductive system

increased prostate gland adenocarcinoma incidence ( J:231906 )

♂ • one mouse at 6 weeks of age shows a microinvasive adenocarcinoma

♂ • mice fed a high-fat diet upon weaning show an increase in the penetrance and number of microinvasive foci of microinvasive adenocarcinoma

increased prostate intraepithelial neoplasia incidence ( J:231906 )

♂ • mice show a similar number of prostate ductules affected by intraepithelial neoplasia (mPIN) as single Pten^tm1Hwu conditional mice

Genotype
MGI:5827768

cn129

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)20Fwan/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * FVB/NCrl

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:238768 )

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

increased prostate intraepithelial neoplasia incidence ( J:238768 )

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

• prostate tissue in 2/8 mutant mice contains large papillary structures with complex glandular architecture

• mice develop a lower grade reactive stroma with lymphocytic infiltration as compared to mice with JAG1 overexpression

neoplasm

increased prostate gland adenocarcinoma incidence ( J:238768 )

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

increased prostate intraepithelial neoplasia incidence ( J:238768 )

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

• prostate tissue in 2/8 mutant mice contains large papillary structures with complex glandular architecture

• mice develop a lower grade reactive stroma with lymphocytic infiltration as compared to mice with JAG1 overexpression

reproductive system

increased prostate gland adenocarcinoma incidence ( J:238768 )

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

increased prostate intraepithelial neoplasia incidence ( J:238768 )

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

• prostate tissue in 2/8 mutant mice contains large papillary structures with complex glandular architecture

• mice develop a lower grade reactive stroma with lymphocytic infiltration as compared to mice with JAG1 overexpression

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:238768

Genotype
MGI:5827766

cn130

• Allelic Composition: Gt(ROSA)26Sor^tm1(JAG1)Xin/Gt(ROSA)26Sor⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Pbsn-cre)20Fwan/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * FVB/NCrl

endocrine/exocrine glands

abnormal prostate gland morphology ( J:238768 )

• increase in number CD45+ leukocytes in prostate tissue as compared to control (lacking JAG1 over expression)

• prostate tissue in 15/16 mutant mice contains large papillary structures with complex glandular architecture

• blood vessel density in prostate is 1.8 fold more than in control

• increased collagen deposition at the prostatic peri-glandular spaces

• presence of reactive stroma

• stromal cell layer is disrupted and thinner with increased vimentin staining in peri-glandular stromal cells

• prostate tissues contain more inflammatory foci as compared to controls (lacking JAG1 overexpression)

increased prostate gland adenocarcinoma incidence ( J:238768 )

• 62.5% mutant mice (as compared to 20% in controls lacking JAG1 overexpression) have a mass of poorly differentiated adenocarcinoma extended into lumen of seminal vesicles and replacing the normal lining of epithelium

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

increased prostate intraepithelial neoplasia incidence ( J:238768 )

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

• mice develop a higher grade reactive stroma with lymphocytic infiltration as compared to control (lacking JAG1 overexpression)

neoplasm

increased prostate gland adenocarcinoma incidence ( J:238768 )

• 62.5% mutant mice (as compared to 20% in controls lacking JAG1 overexpression) have a mass of poorly differentiated adenocarcinoma extended into lumen of seminal vesicles and replacing the normal lining of epithelium

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

increased prostate intraepithelial neoplasia incidence ( J:238768 )

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

• mice develop a higher grade reactive stroma with lymphocytic infiltration as compared to control (lacking JAG1 overexpression)

reproductive system

abnormal prostate gland morphology ( J:238768 )

• increase in number CD45+ leukocytes in prostate tissue as compared to control (lacking JAG1 over expression)

• prostate tissue in 15/16 mutant mice contains large papillary structures with complex glandular architecture

• blood vessel density in prostate is 1.8 fold more than in control

• increased collagen deposition at the prostatic peri-glandular spaces

• presence of reactive stroma

• stromal cell layer is disrupted and thinner with increased vimentin staining in peri-glandular stromal cells

• prostate tissues contain more inflammatory foci as compared to controls (lacking JAG1 overexpression)

increased prostate gland adenocarcinoma incidence ( J:238768 )

• 62.5% mutant mice (as compared to 20% in controls lacking JAG1 overexpression) have a mass of poorly differentiated adenocarcinoma extended into lumen of seminal vesicles and replacing the normal lining of epithelium

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

increased prostate intraepithelial neoplasia incidence ( J:238768 )

• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year

• mice develop a higher grade reactive stroma with lymphocytic infiltration as compared to control (lacking JAG1 overexpression)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:238768

Genotype
MGI:4836596

cn131

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

mortality/aging

premature death ( J:96296 )

• survival of majority of mice is 10-20 weeks after intrabursal injection of an adenovirus expressing Cre

neoplasm

increased metastatic potential ( J:96296 )

• 43% of ovarian tumors metastasize to the lungs

increased endometrial carcinoma incidence ( J:96296 )

♀ • primary tumor is located in the ovary

♀ • tumors are solid and cystic and diagnosed as ovarian edometrioid adenocarcinomas

♀ • 7 weeks after intrabursal injection through the infundibulum of an adenovirus expressing Cre, mice, mutants develop endometrioid ovarian cancer

reproductive system

increased endometrial carcinoma incidence ( J:96296 )

♀ • 7 weeks after intrabursal injection through the infundibulum of an adenovirus expressing Cre, mice, mutants develop endometrioid ovarian cancer

♀ • primary tumor is located in the ovary

♀ • tumors are solid and cystic and diagnosed as ovarian edometrioid adenocarcinomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:96296

Genotype
MGI:4941739

cn132

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Gdf9-icre)5092Coo/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

endocrine/exocrine glands

abnormal primordial ovarian follicle morphology ( J:155357 )

♀ • mutant females exhibit accelerated activation of primordial follicles

reproductive system

abnormal primordial ovarian follicle morphology ( J:155357 )

♀ • mutant females exhibit accelerated activation of primordial follicles

Genotype
MGI:5013920

cn133

• Allelic Composition: Pdpk1^tm1Maka/Pdpk1^tm1Maka; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Zp3-cre)93Knw/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

reproductive system

reproductive system phenotype ( J:165798 )

N • fertility of double mutant females is completely restored from 10-30 weeks of age when mated with wild-type males compared to single conditional homozygous Pdpk1 mutants

N • embryos derived from double mutant females mated with wild-type males show normal perimplantation development, indicating rescue of the two-cell arrest and the suppressed embryonic genome activation seen in embryos from single conditional homozygous Pdpk1 mutants

Genotype
MGI:4941741

cn134

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tsc1^tm1Djk/Tsc1^tm1Djk; Tg(Gdf9-icre)5092Coo/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

endocrine/exocrine glands

abnormal ovarian follicle morphology ( J:155357 )

♀ • mutants exhibit premature activation of the entire primordial follicle pool with an enhanced rate of oocyte growth and follicular development greater than in either single mutant

reproductive system

abnormal ovarian follicle morphology ( J:155357 )

♀ • mutants exhibit premature activation of the entire primordial follicle pool with an enhanced rate of oocyte growth and follicular development greater than in either single mutant

Genotype
MGI:5816458

cn135

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Adipoq-cre)1Evdr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * FVB/NJ

neoplasm

neoplasm ( J:237232 )

N • mice do not develop liposarcomas

Genotype
MGI:3813526

cn136

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(KRT14-cre)#Smr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * SJL/J

mortality/aging

premature death ( J:138927 )

• mice exhibit decreased survival compared to wild type mice

neoplasm

increased mammary gland tumor incidence ( J:138927 )

• 36% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors

• mammary gland tumors exhibit prominent intraluminal and ductal proliferation

• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis

increased mammary adenocarcinoma incidence ( J:138927 )

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:138927 )

• 36% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors

• mammary gland tumors exhibit prominent intraluminal and ductal proliferation

• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis

increased mammary adenocarcinoma incidence ( J:138927 )

integument

increased mammary gland tumor incidence ( J:138927 )

• 36% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors

• mammary gland tumors exhibit prominent intraluminal and ductal proliferation

• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis

increased mammary adenocarcinoma incidence ( J:138927 )

Genotype
MGI:3813525

cn137

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(KRT14-cre)#Smr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * SJL/J

mortality/aging

decreased survivor rate ( J:138927 )

• 40% of mice survive weaning if littermate competition is removed and the weaning period is extended

premature death ( J:138927 )

• mice that survive weaning do not live beyond 250 days

• however, survival can be increased by treatment with rapamycin

postnatal lethality, incomplete penetrance ( J:138927 )

• mice die rapidly in the first few days of life

• however, lifespan can be increased if littermate competition is removed and the weaning period is extended

neoplasm

increased thyroid tumor incidence ( J:138927 )

• 12% of mice develop thyroid tumors with a follicular aspect

increased mammary gland tumor incidence ( J:138927 )

• 11% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors

• mammary gland tumors exhibit prominent intraluminal and ductal proliferation

• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis

increased mammary adenocarcinoma incidence ( J:138927 )

increased skin tumor incidence ( J:138927 )

• mice develop multiple hyperproliferative skin lesions that range from mucocutaneous lesions to tumor formation

increased skin papilloma incidence ( J:138927 )

• mice develop papules around the nose, mouth and eyes

endocrine/exocrine glands

enlarged thyroid gland ( J:138927 )

• 56% of mice develop multinodular goiters

increased thyroid tumor incidence ( J:138927 )

• 12% of mice develop thyroid tumors with a follicular aspect

abnormal nipple morphology ( J:138927 )

♀ • in 80% of mice

increased mammary gland tumor incidence ( J:138927 )

• 11% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors

• mammary gland tumors exhibit prominent intraluminal and ductal proliferation

• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis

increased mammary adenocarcinoma incidence ( J:138927 )

integument

abnormal nipple morphology ( J:138927 )

♀ • in 80% of mice

increased mammary gland tumor incidence ( J:138927 )

• 11% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors

• mammary gland tumors exhibit prominent intraluminal and ductal proliferation

• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis

increased mammary adenocarcinoma incidence ( J:138927 )

abnormal hair shaft morphology ( J:138927 )

• at 11 days, the hair shafts have a disheveled appearance unlike in heterozygous mice

enlarged hair follicles ( J:138927 )

• hair follicles are increased in size compared to in wild type mice

abnormal vibrissa follicle morphology ( J:138927 )

• facial and periauricular lesions involve hyperproliferation of the outer root sheath in the vibrissae

hyperkeratosis ( J:138927 )

• papillomatous lesions of the skin exhibit hyperkeratosis and acanthosis through the face and body skin

acanthosis ( J:138927 )

• papillomatous lesions of the skin exhibit hyperkeratosis and acanthosis through the face and body skin

flaky skin ( J:138927 )

• at 6 days of age

skin lesions ( J:138927 )

• mice develop multiple hyperproliferative skin lesions that range from mucocutaneous lesions to tumor formation

• facial and periauricular lesions involve hyperproliferation of the outer root sheath and vibrissae

• acral extremities areas exhibit verrucous and hyperkeratotic lesions also seen in the punctuate palmoplantar keratosis of the paws

• mice exhibit palmoplantar keratoses, acral keratosis and oral papules

• cutaneous lesions contain trichilemmomas

• however, rapamycin treatment reverses and prevents lesion formation

wrinkled skin ( J:138927 )

• at 6 days of age

increased skin tumor incidence ( J:138927 )

• mice develop multiple hyperproliferative skin lesions that range from mucocutaneous lesions to tumor formation

increased skin papilloma incidence ( J:138927 )

• mice develop papules around the nose, mouth and eyes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cowden syndrome		DOID:6457	OMIM:PS158350	J:138927

Genotype
MGI:4829793

cn138

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(MMTV-cre)4Mam/0
• Genetic Background: involves: 129S4/SvJae * FVB

endocrine/exocrine glands

abnormal branching of the mammary ductal tree ( J:78415 )

♀ • transplanted mammary epithelium exhibits more and feather-like irregular side-branches in ductal and terminal structures compared with controls

mammary gland duct hyperplasia ( J:78415 )

♀ • transplants from virgins exhibit focal ductal hyperplasia containing papillary structure

♀ • after one pregnancy, transplants exhibit intra-luminal focal hyperplasia

integument

abnormal branching of the mammary ductal tree ( J:78415 )

♀ • transplanted mammary epithelium exhibits more and feather-like irregular side-branches in ductal and terminal structures compared with controls

mammary gland duct hyperplasia ( J:78415 )

♀ • transplants from virgins exhibit focal ductal hyperplasia containing papillary structure

♀ • after one pregnancy, transplants exhibit intra-luminal focal hyperplasia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cowden syndrome		DOID:6457	OMIM:PS158350	J:78415

Genotype
MGI:4944271

cn139

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129S4/SvJae * FVB

muscle

enhanced skeletal muscle regeneration ( J:169364 )

• in mice fed a normal diet, the weights of injured tibialis anterior muscles are greater than weights of muscles in controls

• regenerating myofibers after injury are larger compared to control injured myofibers, indicating that mutants exhibit a promotion in regeneration of injured muscles

• after 8 months of a high-fat diet, mutants exhibit larger myofiber sizes of regenerating muscles at 6 and 12 days after injury and increased weights of the injured tibialis anterior muscles than controls

• after 8 months on a high-fat diet, collagen deposition is reduced in regenerating muscles compared to controls

homeostasis/metabolism

decreased circulating glucose level ( J:169364 )

• after 8 months of a high-fat diet, mutants exhibit lower glucose levels than controls on the same diet

decreased circulating insulin level ( J:169364 )

• after 8 months of a high-fat diet, mutants exhibit lower insulin levels than controls on the same diet

Genotype
MGI:4882047

cn140

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
• Genetic Background: involves: 129S4/SvJae * FVB/N

cardiovascular system

abnormal response to cardiac infarction ( J:149180 )

• hearts of mutants treated with tamoxifen for 3 weeks to induce cre-expression develop significantly better function recovery in response to 30 min ischemia followed by 120 min reperfusion than controls, showing significantly improved end-diastolic pressure, left ventricle developed pressure (LVDP) and LVDP recoveries, and improved systolic and diastolic contractility of hearts

• at 60 min post reperfusion, recovery of left ventricular diastolic pressure reaches 77.9% of pre-ischemia in hearts versus 44% in controls

• hearts have significantly fewer apoptosis positive cardiomyocytes after ischemia/reperfusion (I/R) injury than controls

decreased myocardial infarct size ( J:149180 )

• mutants treated with tamoxifen to induce cre-expression exhibit a significant reduction in infarct size after ischemia

homeostasis/metabolism

abnormal response to cardiac infarction ( J:149180 )

• hearts of mutants treated with tamoxifen for 3 weeks to induce cre-expression develop significantly better function recovery in response to 30 min ischemia followed by 120 min reperfusion than controls, showing significantly improved end-diastolic pressure, left ventricle developed pressure (LVDP) and LVDP recoveries, and improved systolic and diastolic contractility of hearts

• at 60 min post reperfusion, recovery of left ventricular diastolic pressure reaches 77.9% of pre-ischemia in hearts versus 44% in controls

• hearts have significantly fewer apoptosis positive cardiomyocytes after ischemia/reperfusion (I/R) injury than controls

decreased myocardial infarct size ( J:149180 )

• mutants treated with tamoxifen to induce cre-expression exhibit a significant reduction in infarct size after ischemia

Genotype
MGI:4839512

cn141

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(MMTV-cre)7Mul/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

neoplasm

neoplasm ( J:133305 )

N • mice do not develop mammary tumors over a 16 month period

Genotype
MGI:4839218

cn142

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Alb1-cre)1Dlr/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

endocrine/exocrine glands

bile duct hyperplasia ( J:111718 )

• 10 of 23 mutants between 2-11 months of age exhibit varying degrees of hyperplasia primarily in larger bile duct

increased cholangiocarcinoma incidence ( J:111718 )

• 6 of 15 mutants between 12-16 months of age have cholangiocellular carcinoma foci, although much fewer of them and smaller ones than in double Smad4 and Pten mutants, and no invasive cholangiocelluar carcinomas were seen

liver/biliary system

bile duct hyperplasia ( J:111718 )

• 10 of 23 mutants between 2-11 months of age exhibit varying degrees of hyperplasia primarily in larger bile duct

increased cholangiocarcinoma incidence ( J:111718 )

• 6 of 15 mutants between 12-16 months of age have cholangiocellular carcinoma foci, although much fewer of them and smaller ones than in double Smad4 and Pten mutants, and no invasive cholangiocelluar carcinomas were seen

increased hepatocellular carcinoma incidence ( J:111718 )

• 1 of 13 and 5 of 15 mutants develop hepatocellular carcinoma at 8-9 months of age and 12-16 months of age, respectively

neoplasm

increased cholangiocarcinoma incidence ( J:111718 )

• 6 of 15 mutants between 12-16 months of age have cholangiocellular carcinoma foci, although much fewer of them and smaller ones than in double Smad4 and Pten mutants, and no invasive cholangiocelluar carcinomas were seen

increased hepatocellular carcinoma incidence ( J:111718 )

• 1 of 13 and 5 of 15 mutants develop hepatocellular carcinoma at 8-9 months of age and 12-16 months of age, respectively

Genotype
MGI:5013915

cn143

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(GZMB-cre)1Jcb/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

immune system

abnormal CD8-positive, alpha-beta T cell physiology ( J:164425 )

• mutants infected with lymphocytic choriomeningitis virus (LCMV) to induce T-cell activation and thus cre-expression exhibit better survival of effector CD8 T cells under serum-starvation conditions compared to controls, but only show modest effects on the expansion and contraction of effector CD8 T cells

• clonal burst of mutant effector CD8 T cells is about 1/2 that of wild-type controls and there is a slight, but not significant reduction in the number of memory T cells that form in lymphoid and nonlymphoid tissues

decreased interleukin-2 secretion ( J:164425 )

• production of IL-2 by CD8 T cells is diminished in mutants infected with LCMV to induce T-cell activation and thus cre-expression

hematopoietic system

abnormal CD8-positive, alpha-beta T cell physiology ( J:164425 )

• mutants infected with lymphocytic choriomeningitis virus (LCMV) to induce T-cell activation and thus cre-expression exhibit better survival of effector CD8 T cells under serum-starvation conditions compared to controls, but only show modest effects on the expansion and contraction of effector CD8 T cells

• clonal burst of mutant effector CD8 T cells is about 1/2 that of wild-type controls and there is a slight, but not significant reduction in the number of memory T cells that form in lymphoid and nonlymphoid tissues

Genotype
MGI:5141742

cn144

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten⁺; Tg(Upk2-cre)6Xrw/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

integument

increased skin papilloma incidence ( J:174242 )

• 42% of mutants develop skin papillomas

neoplasm

increased skin papilloma incidence ( J:174242 )

• 42% of mutants develop skin papillomas

Genotype
MGI:4830362

cn145

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

mortality/aging

lethality at weaning, complete penetrance ( J:100428 )

• death occurs around P21

nervous system

abnormal cerebellum development ( J:100428 )

• cerebella layering defects

• before P3, cerebella are enlarged but the external granule layer (EGL) and cerebellar lobules are normal and Purkinje cell position is normal

• however, after P6, mutants show a marked cerebellar enlargement and lack internal granule layer and folia

abnormal cerebellar foliation ( J:100428 )

• loss of foliation after P6

increased brain size ( J:100428 )

abnormal cerebellar Purkinje cell layer ( J:100428 )

• Purkinje layer defect is first seen at P4-P6 and by P9, numerous Purkinje neurons are randomly scattered

abnormal Bergmann glial cell morphology ( J:100428 )

• disruption of Bergmann glial layering

abnormal Bergmann glial cell differentiation ( J:100428 )

• premature differentiation of Bergmann glia leading to extensive layering defects

ectopic Bergmann glia cells ( J:100428 )

• some Bergmann cell bodies are randomly distributed at P7 and lose their contacts to the pial surface and are positioned deep within the internal granule layer region

ectopic Purkinje cell ( J:100428 )

• Purkinje cell layer is normal at P3 but there are many ectopic Purkinje cells by P9

abnormal cerebellar granule layer morphology ( J:100428 )

• lack of an organized internal granule layer (IGL) at P6

• severe granule neuron layering defects

abnormal cerebellar granule cell morphology ( J:100428 )

• mutants exhibit granule neuron migration defects, with granule neurons failing to migrate to the internal granule layer and accumulating in the molecular layer (ML)

• granule neurons are resistant to low potassium-induced cell death under serum deprivation conditions

enlarged cerebellum ( J:100428 )

cellular

abnormal Bergmann glial cell differentiation ( J:100428 )

• premature differentiation of Bergmann glia leading to extensive layering defects

growth/size/body

megacephaly ( J:100428 )

Genotype
MGI:4829794

cn146

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Nes-cre)1Atp/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:73255 )

• die shortly after birth

nervous system

abnormal brain morphology ( J:73255 )

• cells from mutant brains are larger

abnormal cortical ventricular zone morphology ( J:73255 )

• increase in cell proliferation in the ventricular zone of E14.5 mutant telencephalon

• decrease in cell death in the ventricular zone of E14.5 mutant telencephalon

increased brain size ( J:73255 )

increased brain weight ( J:73255 )

• brain weight is increased at E14, E18, and at birth

• brain weight at birth is double that of wild-type

abnormal brainstem morphology ( J:73255 )

• nuclei in the brainstem are not identifiable

abnormal hippocampus layer morphology ( J:73255 )

• the laminar pattern of the hippocampus is disturbed

abnormal cerebellum morphology ( J:73255 )

• the laminar pattern of the cerebellum is disturbed

absent cerebellar foliation ( J:73255 )

increased neuronal precursor cell number ( J:73255 )

• cortex cells from E14.5 brains cultured at moderate or clonal density exhibit a significantly greater number of neurospheres than wild-type cells, indicating an increase in stem/progenitor cells in mutants

vision/eye

eyelids open at birth ( J:73255 )

growth/size/body

megacephaly ( J:73255 )

Genotype
MGI:4882148

cn147

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Ddx4-cre)1Dcas/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

endocrine/exocrine glands

enlarged ovary ( J:138697 )

♀ • ovaries are enlarged by P21 due to global primordial follicle activation

abnormal ovary physiology ( J:138697 )

♀ • ovaries explanted at birth and cultured for 8 days grow more rapidly than controls

reproductive system

enlarged ovary ( J:138697 )

♀ • ovaries are enlarged by P21 due to global primordial follicle activation

abnormal ovary physiology ( J:138697 )

♀ • ovaries explanted at birth and cultured for 8 days grow more rapidly than controls

reduced female fertility ( J:138697 )

♀ • females exhibit a dramatic age-dependent decrease in fertility and have no more than two litters

growth/size/body

enlarged ovary ( J:138697 )

♀ • ovaries are enlarged by P21 due to global primordial follicle activation

Genotype
MGI:4882150

cn148

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Ddx4-cre/ERT2)1Dcas/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

endocrine/exocrine glands

abnormal primordial ovarian follicle morphology ( J:138697 )

♀

enlarged ovary ( J:138697 )

♀

reproductive system

abnormal primordial ovarian follicle morphology ( J:138697 )

♀

enlarged ovary ( J:138697 )

♀

growth/size/body

enlarged ovary ( J:138697 )

♀

Genotype
MGI:4844083

cn149

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Fabp1-cre)1Jig/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

digestive/alimentary system

increased colon adenocarcinoma incidence ( J:106662 )

mortality/aging

premature death ( J:106662 )

• only 45% of males survive to 13.5 months of age, compared to 75% of females surviving to this age

endocrine/exocrine glands

prostate gland anterior lobe hyperplasia ( J:106662 )

♂ • hyperplasia in the anterior prostate is observed at 8 days of age

increased prostate gland tumor incidence ( J:106662 )

♂ • within the first year of life, 97% of males develop tumors of the anterior prostate

♂ • prostate tumors are carcinomas

♂ • in males over one year of age, the tumor takes over the entire prostate and seminal vesicle

renal/urinary system

abnormal renal/urinary system morphology ( J:106662 )

• hyperplasia in the urinary tract

increased renal carcinoma incidence ( J:106662 )

• urothelial carcinoma of the kidney

increased urinary bladder carcinoma incidence ( J:106662 )

• urothelial carcinoma of the bladder

• 22% of mutants exhibit bladder cancer by 13.5 months of age

increased urethra carcinoma incidence ( J:106662 )

hydronephrosis ( J:106662 )

• males exhibit hydronephrosis of the kidney

abnormal urinary bladder urothelium morphology ( J:106662 )

• epithelial hypertrophy and nuclear atypia are evident in bladders at birth

• 100% penetrance of hypertrophy and hyperplasia in the bladder by 6 weeks of age

abnormal urination ( J:106662 )

♂ • 1/3 of male deaths are due to inability to urinate due to urinary tract blockage

♂ • females do not lose the ability to urinate

reproductive system

prostate gland anterior lobe hyperplasia ( J:106662 )

♂ • hyperplasia in the anterior prostate is observed at 8 days of age

increased prostate gland tumor incidence ( J:106662 )

♂ • within the first year of life, 97% of males develop tumors of the anterior prostate

♂ • prostate tumors are carcinomas

♂ • in males over one year of age, the tumor takes over the entire prostate and seminal vesicle

neoplasm

increased prostate gland tumor incidence ( J:106662 )

♂ • within the first year of life, 97% of males develop tumors of the anterior prostate

♂ • prostate tumors are carcinomas

♂ • in males over one year of age, the tumor takes over the entire prostate and seminal vesicle

increased metastatic potential ( J:106662 )

• metastasis of the bladder and urothelial carcinomas is observed

increased carcinoma incidence ( J:106662 )

• urothelial carcinoma of the bladder, ureter, and kidney

• squamous cell carcinoma of the vagina and rectum

• carcinomas of the prostate, seminal vesicles and urethra

increased colon adenocarcinoma incidence ( J:106662 )

increased renal carcinoma incidence ( J:106662 )

• urothelial carcinoma of the kidney

increased squamous cell carcinoma incidence ( J:106662 )

• 41% of females develop vaginal squamous cell carcinoma

increased urinary bladder carcinoma incidence ( J:106662 )

• urothelial carcinoma of the bladder

• 22% of mutants exhibit bladder cancer by 13.5 months of age

increased urethra carcinoma incidence ( J:106662 )

Genotype
MGI:5294347

cn150

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129S4/SvJae * FVB/NCr

endocrine/exocrine glands

enlarged thyroid gland ( J:177181 )

• enlarged in a smooth and symmetrical manner with abundant colloid

Genotype
MGI:5294346

cn151

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(CAG-EGFP,-PAX8/PPARG)1Rkoe/0; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129S4/SvJae * FVB/NCr * FVB/NJ

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:177181 )

• pioglitazone-fed mice exhibit lipid accumulation in thyroid cells

enlarged thyroid gland ( J:177181 )

• 100-fold increase in size

• larger than in Pten^tm1Hwu/Pten^tm1Hwu Tg(TPO-cre)1Shk mice

• irregularly shaped, mutlinodular, more cellular than colloid

• however, pioglitazone (a PPARG inhibitor) decreases thyroid size

increased thyroid carcinoma incidence ( J:177181 )

• with metastasis to the lungs and soft tissues

• however, pioglitazone (a PPARG inhibitor) induces a lipogenic antitumor response

abnormal thymus physiology ( J:177181 )

• pioglitazone-fed mice exhibit decreased thyroid size due to increased apoptosis

homeostasis/metabolism

increased circulating thyroxine level ( J:177181 )

• 6-fold

• however, pioglitazone normalizes thyroid function

increased circulating triiodothyronine level ( J:177181 )

• 3.5-fold

• however, pioglitazone normalizes thyroid function

neoplasm

increased thyroid carcinoma incidence ( J:177181 )

• with metastasis to the lungs and soft tissues

• however, pioglitazone (a PPARG inhibitor) induces a lipogenic antitumor response

immune system

abnormal thymus physiology ( J:177181 )

• pioglitazone-fed mice exhibit decreased thyroid size due to increased apoptosis

hematopoietic system

abnormal thymus physiology ( J:177181 )

• pioglitazone-fed mice exhibit decreased thyroid size due to increased apoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid gland carcinoma		DOID:3963		J:177181

Genotype
MGI:4839497

cn152

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Vhl^tm1Jae/Vhl^tm1Jae; Tg(Cdh16-cre)91Igr/0
• Genetic Background: involves: 129S4/SvJae * ICR

reproductive system

abnormal oviduct morphology ( J:137442 )

♀ • cysts and squamous epithelial hyperplasia in the oviduct

endometrium hyperplasia ( J:137442 )

♀ • females exhibit hyperplasia and full squamous differentiation of the uterine endometrial lumen, endometrial hyperplasia, and endometrial hyperplasia with cyst formation

abnormal uterine cervix squamous epithelium morphology ( J:137442 )

♀ • cysts and squamous epithelial hyperplasia in the cervix

abnormal epididymis morphology ( J:137442 )

♂ • squamous metaplasia is seen in the epididymis

♂ • vascularization is increased in the epididymides

increased epididymal cystadenoma incidence ( J:137442 )

♂ • tumors contain regions of cystadenoma characterized by adenoid structures identical to human cystadenoma lesions arising in epididymides

♂ • cystadenoma display clear cell morphology

neoplasm

increased tumor incidence ( J:137442 )

• regions of squamous differentiation intermingle with the regions of cystadenoma

• cystadenomas appear to result from basal cell proliferation without differentiation, whereas regions of squamous metaplasia contain abundant basal cells in basal layers as well as cells with markers of epidermal differentiation

increased adenoma incidence ( J:137442 )

• all mutants develop benign mixed adenosquamous genital tract tumors (in epididymis, vesicular glands, vas deferens, endometrium, and oviduct) resembling clear cell cystadenomas that form in patients with Von Hippel-Lindau syndrome (VHL)

• tumors arise simultaneously in all genital tract epithelia and show expansion of basal cells

• endometrial hyperplasia with cyst formation resembles cystadenoma and cystic lesions seen in broad ligament of females with VHL

increased epididymal cystadenoma incidence ( J:137442 )

♂ • tumors contain regions of cystadenoma characterized by adenoid structures identical to human cystadenoma lesions arising in epididymides

♂ • cystadenoma display clear cell morphology

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
von Hippel-Lindau disease		DOID:14175	OMIM:193300	J:137442

Genotype
MGI:4839499

cn153

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Cdh16-cre)91Igr/0
• Genetic Background: involves: 129S4/SvJae * ICR

endocrine/exocrine glands

abnormal seminal vesicle morphology ( J:137442 )

♂ • epithelial hyperplasia in vesicular glands

reproductive system

abnormal reproductive system morphology ( J:137442 )

• genital tissues are enlarged

abnormal seminal vesicle morphology ( J:137442 )

♂ • epithelial hyperplasia in vesicular glands

abnormal endometrium morphology ( J:137442 )

♀ • endometrial hyperplasia is accompanied by partial squamous differentiation

endometrium hyperplasia ( J:137442 )

♀ • hyperplasia of the endometrial glands and lumen

abnormal epididymis epithelium morphology ( J:137442 )

♂ • epithelial hyperplasia in epididymis

abnormal vas deferens morphology ( J:137442 )

♂ • epithelial hyperplasia in vas deferens

neoplasm

neoplasm ( J:137442 )

N • mice up to 1 year of age do not form tumors

Genotype
MGI:5008633

cn154

• Allelic Composition: Gt(ROSA)26Sor^tm2Thl/Gt(ROSA)26Sor⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tyr^c-Brd/Tyr^c-Brd
• Genetic Background: involves: 129/Sv * 129S4/SvJae * C57BL/6

mortality/aging

premature death ( J:172585 )

• median survival is 85 days following injection of PDGF and cre compared with 27 days for similarly treated Pten^tm1Hwu Trp53^tm1Thl double homozygotes

neoplasm

increased glioblastoma incidence ( J:172585 )

• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells

nervous system

increased glioblastoma incidence ( J:172585 )

• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
glioblastoma proneural subtype		DOID:0050804		J:172585

Genotype
MGI:5008634

cn155

• Allelic Composition: Gt(ROSA)26Sor^tm2Thl/Gt(ROSA)26Sor⁺; Pten^tm1Hwu/Pten^tm1Hwu; Trp53^tm1Thl/Trp53^tm1Thl; Tyr^c-Brd/Tyr^c-Brd
• Genetic Background: involves: 129/Sv * 129S4/SvJae * C57BL/6

mortality/aging

premature death ( J:172585 )

• median survival is 27 days following injection of PDGF and cre compared with 85 days for similarly treated Pten^tm1Hwu homozygotes

neoplasm

increased tumor growth/size ( J:172585 )

• following injection of PDGF and cre, tumor growth is increased compared to in similarly treated Pten^tm1Hwu homozygotes

increased glioblastoma incidence ( J:172585 )

• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells

nervous system

increased glioblastoma incidence ( J:172585 )

• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
glioblastoma proneural subtype		DOID:0050804		J:172585

Genotype
MGI:3837855

cn156

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Col1a1^{tm1(CAG-EGFR)Char}/Col1a1^{tm1(CAG-EGFR)Char}; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL

mortality/aging

decreased tumor-free survival time ( J:146494 )

• 10% of mice die from glioblastoma multiforme development following intracranial injection of an adenoviral cre unlike similarly treated Col1a1^{tm1(CAG-EGFR)Char} homozygotes that do not develop tumors

neoplasm

increased glioblastoma incidence ( J:146494 )

• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with a greater than 90% tumor-free survival past 30 weeks unlike similarly treated Col1a1^{tm1(CAG-EGFR)Char} homozygotes that do not develop tumors

nervous system

increased glioblastoma incidence ( J:146494 )

• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with a greater than 90% tumor-free survival past 30 weeks unlike similarly treated Col1a1^{tm1(CAG-EGFR)Char} homozygotes that do not develop tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
high grade glioma		DOID:3070	OMIM:PS137800	J:146494

Genotype
MGI:3837856

cn157

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Col1a1^{tm2(CAG-EGFR*)Char}/Col1a1^{tm2(CAG-EGFR*)Char}; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL

mortality/aging

decreased tumor-free survival time ( J:146494 )

• no mice surviving tumor-free beyond 10 weeks following intracranial injection of an adenoviral cre unlike similarly treated Col1a1^{tm2(CAG-EGFR*)Char} homozygotes that do not develop tumors

neoplasm

increased glioblastoma incidence ( J:146494 )

• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 10 weeks unlike similarly treated Col1a1^{tm2(CAG-EGFR*)Char} homozygotes that do not develop tumors

nervous system

increased glioblastoma incidence ( J:146494 )

• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 10 weeks unlike similarly treated Col1a1^{tm2(CAG-EGFR*)Char} homozygotes that do not develop tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
high grade glioma		DOID:3070	OMIM:PS137800	J:146494

Genotype
MGI:3837857

cn158

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Col1a1^{tm1(CAG-EGFR)Char}/Col1a1^{tm2(CAG-EGFR*)Char}; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL

mortality/aging

decreased tumor-free survival time ( J:146494 )

• no mice surviving tumor-free beyond 15 weeks following intracranial injection of an adenoviral cre unlike similarly treated Col1a1^{tm2(CAG-EGFR*)Char} or Col1a1^{tm1(CAG-EGFR)Char} homozygotes that do not develop tumors

neoplasm

increased glioblastoma incidence ( J:146494 )

• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 13 weeks unlike similarly treated Col1a1^{tm2(CAG-EGFR*)Char} or Col1a1^{tm1(CAG-EGFR)Char} homozygotes that do not develop tumors

nervous system

increased glioblastoma incidence ( J:146494 )

• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 13 weeks unlike similarly treated Col1a1^{tm2(CAG-EGFR*)Char} or Col1a1^{tm1(CAG-EGFR)Char} homozygotes that do not develop tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
high grade glioma		DOID:3070	OMIM:PS137800	J:146494

Genotype
MGI:5427585

cx159

• Allelic Composition: Pik3ca^tm1.1Waph/Pik3ca⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * BALB/c * C57BL/6

Ovary tumors in Pik3ca^tm1.1Waph/Pik3ca^tm1.1Waph Pten^tm1Hwu/Pten^tm1Hwu mice

mortality/aging

premature death ( J:184382 )

• of mice infected with a cre-expressing adenovirus due to ovarian masses with a median latency of 16 weeks

• however, treatment with an ATP-competitive PI3K/mTOR inhibitor, PF04691502 extends survival time

reproductive system

abnormal ovary morphology ( J:184382 )

♀ • the ovarian surface epithelium of mice infected with a cre-expressing adenovirus exhibit marked hyperplasia compared with control mice

♀ • mice infected with a cre-expressing adenovirus exhibit ovarian masses and show varying degrees of fibrous and/or smooth muscle hyperplasia compared with control mice

increased ovary tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas, ovarian granulosa cell tumors and a single ovarian luteoma compared with control mice

increased granulosa cell tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian granulosa cell tumors compared with control mice

abnormal ovary physiology ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus exhibit ovarian surface epithelium hyperproliferative changes compared with control mice

ovary hemorrhage ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice

neoplasm

increased ovary tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas, ovarian granulosa cell tumors and a single ovarian luteoma compared with control mice

increased granulosa cell tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian granulosa cell tumors compared with control mice

increased adenocarcinoma incidence ( J:184382 )

• mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas compared with control mice

growth/size/body

abnormal peritoneum morphology ( J:184382 )

• mice infected with a cre-expressing adenovirus exhibit intraperitoneal masses on the peritoneal wall and diaphragm masses compared with control mice

homeostasis/metabolism

hemorrhagic ascites ( J:184382 )

• mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice

cardiovascular system

ovary hemorrhage ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice

endocrine/exocrine glands

abnormal ovary morphology ( J:184382 )

♀ • the ovarian surface epithelium of mice infected with a cre-expressing adenovirus exhibit marked hyperplasia compared with control mice

♀ • mice infected with a cre-expressing adenovirus exhibit ovarian masses and show varying degrees of fibrous and/or smooth muscle hyperplasia compared with control mice

increased ovary tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas, ovarian granulosa cell tumors and a single ovarian luteoma compared with control mice

increased granulosa cell tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian granulosa cell tumors compared with control mice

abnormal ovary physiology ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus exhibit ovarian surface epithelium hyperproliferative changes compared with control mice

ovary hemorrhage ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice

muscle

abnormal diaphragm morphology ( J:184382 )

• mice infected with a cre-expressing adenovirus exhibit intraperitoneal masses on the peritoneal wall and diaphragm masses compared with control mice