Phenotypes associated with this allele

• Allele Symbol: Rag1^tm1Mom
• Allele Name: targeted mutation 1, Peter Mombaerts
• Allele ID: MGI:1857241
• Summary: 71 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rag1^tm1Mom/Rag1^tm1Mom	B6.129S7-Rag1^tm1Mom	MGI:3582287
hm2	Rag1^tm1Mom/Rag1^tm1Mom	B6.129S7-Rag1^tm1Mom/J	MGI:7432330
hm3	Rag1^tm1Mom/Rag1^tm1Mom	C.129S7(B6)-Rag1^tm1Mom/Tvg	MGI:7764756
hm4	Rag1^tm1Mom/Rag1^tm1Mom	involves: 129S7/SvEvBrd	MGI:3850561
hm5	Rag1^tm1Mom/Rag1^tm1Mom	involves: 129S7/SvEvBrd * C57BL/10	MGI:3818487
hm6	Rag1^tm1Mom/Rag1^tm1Mom	involves: 129S7/SvEvBrd * C57BL/6	MGI:3767321
hm7	Rag1^tm1Mom/Rag1^tm1Mom	involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD	MGI:3687168
hm8	Rag1^tm1Mom/Rag1^tm1Mom	involves: 129S7/SvEvBrd * CD-1	MGI:2429492
hm9	Rag1^tm1Mom/Rag1^tm1Mom	NOD.129S7(B6)-Rag1^tm1Mom	MGI:3764009
cn10	Gt(ROSA)26Sor^tm1(DTA)Lky/? Il5^tm1.1(icre)Lky/Il5^+ Rag1^tm1Mom/Rag1^tm1Mom	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:5558890
cn11	Foxo1^tm1Flv/Foxo1^tm1Flv Rag1^tm1Mom/Rag1^tm1Mom Tg(CD2-Il7r)1Asin/? Tg(Cd4-cre)1Cwi/? Tg(TcraTcrb)425Cbn/?	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * DBA/2	MGI:3840971
cn12	Foxo1^tm1Flv/Foxo1^tm1Flv Rag1^tm1Mom/Rag1^tm1Mom Tg(Cd4-cre)1Cwi/? Tg(TcraTcrb)425Cbn/?	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * DBA/2	MGI:3840970
cn13	Pdpn^tm2.1Mlkn/Pdpn^tm2.1Mlkn Rag1^tm1Mom/Rag1^tm1Mom Tg(Pdgfrb-cre)9Rha/0	involves: 129S7/SvEvBrd * C57BL/6	MGI:5552953
cn14	Nlrp3^tm1Hhf/Nlrp3^+ Rag1^tm1Mom/Rag1^tm1Mom Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129/Sv * 129P2/OlaHsd * C57BL/6	MGI:3850056
cn15	Ctps1^tm1c(KOMP)Wtsi/Ctps1^tm1c(KOMP)Wtsi Tg(Cd4-cre)1Cwi/0 Foxp3^sf/Y Rag1^tm1Mom/Rag1^+	mixed	MGI:7659107
cx16	Man2a1^tm1Jxm/Man2a1^tm1Jxm Rag1^tm1Mom/Rag1^tm1Mom	B6.129-Rag1^tm1Mom Man2a1^tm1Jxm	MGI:3850631
cx17	Mpz^tm1Msch/Mpz^+ Rag1^tm1Mom/Rag1^tm1Mom	B6.129S7-Mpz^tm1Msch Rag1^tm1Mom	MGI:4947955
cx18	Cd160^tm1Yxf/Cd160^tm1Yxf Rag1^tm1Mom/Rag1^tm1Mom	B6.Cg-Rag1^tm1Mom Cd160^tm1Yxf	MGI:5702315
cx19	Clec2h^tm1.1Apma/Clec2h^tm1.1Apma Rag1^tm1Mom/Rag1^tm1Mom	B6.Cg-Rag1^tm1Mom Clec2h^tm1.1Apma	MGI:7262906
cx20	Rag1^tm1Mom/Rag1^tm1Mom Tg(Tcra,Tcrb)HRCAll/0	B6.Cg-Rag1^tm1Mom Tg(Tcra,Tcrb)HRCAll	MGI:3845009
cx21	H2^u/H2^u Rag1^tm1Mom/Rag1^tm1Mom Tg(Tcra19,Tcrb19)#Stl/0	either: (involves: 129S7/SvEvBrd * C57BL/6 * PL/J) or (involves: 129S7/SvEvBrd * C57BL/6 * C57BL/10 * PL/J)	MGI:6305814
cx22	Rag1^tm1Mom/Rag1^tm1Mom Tyrp1^B-w/Tyrp1^B-w X/Tg(Tcra,Tcrb)9Rest	involves: 101/Rl * 129S7/SvEvBrd * C3H/Rl * C57BL/6	MGI:3826833
cx23	Pld4^tm1.2Nemz/Pld4^tm1.2Nemz Rag1^tm1Mom/Rag1^tm1Mom	involves: 129 * 129S7/SvEvBrd * C57BL/6J * FVB/N	MGI:6452104
cx24	Itk^tm1Ljb/Itk^tm1Ljb Rag1^tm1Mom/Rag1^tm1Mom Tg(Tcra5CC7,Tcrb5CC7)IWep/?	involves: 129 * C57BL/10	MGI:4354514
cx25	Rag1^tm1Mom/Rag1^tm1Mom Slc46a2^tm1Moki/Slc46a2^+ Tg(TcraB12,TcrbB12)1Rest/0	involves: 129 * C57BL/6	MGI:3812196
cx26	Ndfip1^Gt(RRD002)Byg/Ndfip1^Gt(RRD002)Byg Rag1^tm1Mom/Rag1^tm1Mom Tg(TcraTcrb)425Cbn/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * BALB/c * C57BL/6	MGI:5550271
cx27	Rag1^tm1Mom/Rag1^tm1Mom Tnfrsf25^tm1Mjo/Tnfrsf25^tm1Mjo	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:3698843
cx28	Rag1^tm1Mom/Rag1^tm1Mom Tnfsf14^tm1Kpf/Tnfsf14^tm1Kpf	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:7277703
cx29	Rag1^tm1Mom/Rag1^tm1Mom Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/10	MGI:3818486
cx30	Ctla4^tm1All/Ctla4^tm1All Rag1^tm1Mom/Rag1^tm1Mom Tg(TcraTcrb)8Rest/0	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6	MGI:4940117
cx31	H2^dlAb1-Ea/H2^dlAb1-Ea Rag1^tm1Mom/Rag1^tm1Mom Tg(HLA-DRA,HLA-DRB5*0101)loKito/0 Tg(TRATL3A6,TRBTL3A6)#Kito/0	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:5635503
cx32	H2^dlAb1-Ea/H2^dlAb1-Ea Rag1^tm1Mom/Rag1^tm1Mom Tg(HLA-DRA,HLA-DRB5*0101)hiKito/0 Tg(TRATL3A6,TRBTL3A6)#Kito/0	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:5635499
cx33	Lck^tm1Mak/Lck^tm1Mak Rag1^tm1Mom/Rag1^+ Tg(Lck-Fyn*Y528F)5525Cjg/0	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:4360345
cx34	H2^g7/H2^g7 Ins2^tm1Jja/Ins2^tm1Jja Rag1^tm1Mom/Rag1^tm1Mom Tg(TcraBDC12-4.1)10Jos/0 Tg(TcrbBDC12-4.1)82Gse/0	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6 * FVB * NOD	MGI:3687167
cx35	Jak3^tm1Ljb/Jak3^tm1Ljb Rag1^tm1Mom/Rag1^tm1Mom	involves: 129S4/SvJae * 129S7/SvEvBrd	MGI:3769348
cx36	Rag1^tm1Mom/Rag1^tm1Mom Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro	involves: 129S4/SvJae * 129S7/SvEvBrd * BALB/cJ * C57BL/6J	MGI:3699096
cx37	Col1a1^tm1(tetO-Fos)Wag/Col1a1^+ Rag1^tm1Mom/Rag1^tm1Mom Tg(KRT5-rtTA)T2D6Sgkd/0	involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:5555860
cx38	Mefv^tm5.1(MEFV)Chae/Mefv^tm5.1(MEFV)Chae Rag1^tm1Mom/Rag1^tm1Mom	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6	MGI:5007931
cx39	Nfil3^tm1Pbro/Nfil3^tm1Pbro Rag1^tm1Mom/Rag1^tm1Mom	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6	MGI:5576255
cx40	Rag1^tm1Mom/Rag1^tm1Mom Rasa3^scat/Rasa3^scat	involves: 129S7/SvEvBrd * BALB/cBy	MGI:5433362
cx41	Plcg2^Ali5/Plcg2^+ Rag1^tm1Mom/Rag1^tm1Mom	involves: 129S7/SvEvBrd * C3HeB/FeJ * C3HeB/FeJ-Plcg2^Ali5	MGI:3578558
cx42	Pstpip2^Lupo/Pstpip2^Lupo Rag1^tm1Mom/Rag1^tm1Mom	involves: 129S7/SvEvBrd * C3HeB/FeJ * C57BL/6J	MGI:3760618
cx43	Rag1^tm1Mom/Rag1^tm1Mom Tg(Lck-Akt1*E40K)E-3Pnt/0	involves: 129S7/SvEvBrd * C3H/He * C57BL/6	MGI:3803975
cx44	Rag1^tm1Mom/Rag1^tm1Mom Xrcc5^tm1Dbr/Xrcc5^tm1Dbr	involves: 129S7/SvEvBrd * C57BL	MGI:3818750
cx45	Rag1^tm1Mom/Rag1^tm1Mom Trp53^tm1Brd/Trp53^tm1Brd	involves: 129S7/SvEvBrd * C57BL	MGI:3818749
cx46	Rag1^tm1Mom/Rag1^tm1Mom Trp53^tm1Brd/Trp53^tm1Brd Xrcc5^tm1Dbr/Xrcc5^tm1Dbr	involves: 129S7/SvEvBrd * C57BL	MGI:3818748
cx47	Rag1^tm1Mom/Rag1^tm1Mom Tg(CAG-Lyn*)#Paau/0	involves: 129S7/SvEvBrd * C57BL/6	MGI:5512886
cx48	Ier3^tm1Mxw/Ier3^tm1Mxw Rag1^tm1Mom/Rag1^tm1Mom	involves: 129S7/SvEvBrd * C57BL/6	MGI:5474627
cx49	H2^b/H2^b Rag1^tm1Mom/Rag1^tm1Mom Tg(Tcra19,Tcrb19)#Stl/0	involves: 129S7/SvEvBrd * C57BL/6	MGI:6305871
cx50	Rag1^tm1Mom/Rag1^tm1Mom Tg(LPV-TAg1135)11Tvd/0 Tg(TcrLCMV)327Sdz/0	involves: 129S7/SvEvBrd * C57BL/6 * DBA/2	MGI:2665134
cx51	Rag1^tm1Mom/Rag1^+ Tg(LPV-TAg1135)11Tvd/0 Tg(TcrLCMV)327Sdz/0	involves: 129S7/SvEvBrd * C57BL/6 * DBA/2	MGI:2665135
cx52	H2^g7/H2^g7 Rag1^tm1Mom/Rag1^tm1Mom Tg(TcraBDC12-4.1)10Jos/0 Tg(TcrbBDC12-4.1)82Gse/0	involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD	MGI:3687164
cx53	H2^g7/H2^q Rag1^tm1Mom/Rag1^tm1Mom Tg(TcraBDC12-4.1)10Jos/0 Tg(TcrbBDC12-4.1)82Gse/0	involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD	MGI:3687165
cx54	H2^q/H2^q Rag1^tm1Mom/Rag1^tm1Mom Tg(TcraBDC12-4.1)10Jos/0 Tg(TcrbBDC12-4.1)82Gse/0	involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD	MGI:3687166
cx55	Rag1^tm1Mom/Rag1^tm1Mom Tg(TcraBDC12-4.1)10Jos/0 Tg(TcrbBDC12-4.1)82Gse/0	involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD	MGI:3687163
cx56	Ctla4^tm1All/Ctla4^tm1All Rag1^tm1Mom/Rag1^tm1Mom Tg(TcrAND)53Hed/0	involves: 129S/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:4940115
cx57	Igh-J^tm1Mcdl/Igh-J^tm1Mcdl Igk-J^tm1Mcdl/Igk-J^tm1Mcdl Rag1^tm1Mom/Rag1^tm1Mom Tg(DO11.10)10Dlo/?	involves: 129S/Sv * BALB/c * C3H * C57BL/6	MGI:3586594
cx58	Rag1^tm1Mom/Rag1^tm1Mom Tnf^tm2Gkl/Tnf^+	involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6	MGI:3622066
cx59	Rag1^tm1Mom/Rag1^tm1Mom Vtcn1^tm1Lpc/Vtcn1^tm1Lpc	involves: 129S/SvEvBrd * 129S7/SvEvBrd * C57BL/6	MGI:3836413
cx60	Bcl6b^tm2Dent/Bcl6b^tm2Dent Rag1^tm1Mom/Rag1^tm1Mom	involves: 129/Sv * 129S7/SvEvBrd * C57BL/6	MGI:3719168
cx61	Rag1^tm1Mom/Rag1^tm1Mom Tg(LPV-TAg1135)11Tvd/0	involves: 129/Sv * C57BL/6 * DBA/2	MGI:2665126
cx62	Rag1^tm1Mom/Rag1^+ Tg(LPV-TAg1135)11Tvd/0	involves: 129/Sv * C57BL/6 * DBA/2	MGI:2665123
cx63	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Rag1^tm1Mom/Rag1^tm1Mom Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell	NOD.Cg-Rag1^tm1Mom H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell	MGI:3687126
cx64	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Rag1^tm1Mom/Rag1^tm1Mom Tg(HLA-DQA1,HLA-DQB1)73Myl/0	NOD.Cg-Rag1^tm1Mom H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)73Myl	MGI:3687028
cx65	Il2rg^tm1Wjl/Y Rag1^tm1Mom/Rag1^tm1Mom	NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ	MGI:3813939
cx66	Ins2^Akita/Ins2^Akita Prf1^tm1Sdz/Prf1^tm1Sdz Rag1^tm1Mom/Rag1^tm1Mom	NOD.Cg-Rag1^tm1Mom Ins2^Akita Prf1^tm1Sdz	MGI:3817776
cx67	Ins2^Akita/Ins2^+ Prf1^tm1Sdz/Prf1^tm1Sdz Rag1^tm1Mom/Rag1^tm1Mom	NOD.Cg-Rag1^tm1Mom Ins2^Akita Prf1^tm1Sdz	MGI:3817777
cx68	Rag1^tm1Mom/Rag1^tm1Mom Prf1^tm1Sdz/Prf1^tm1Sdz	NOD.Cg-Rag1^tm1Mom Prf1^tm1Sdz/Sz	MGI:3580416
cx69	Prf1^tm1Sdz/Prf1^tm1Sdz Rag1^tm1Mom/Rag1^tm1Mom	NOD.Cg-Rag1^tm1Mom Prf1^tm1Sdz/SzJ	MGI:3844697
cx70	Rag1^tm1Mom/Rag1^tm1Mom Tg(TcraAI4)1Dvs/0 Tg(TcrbAI4)1Dvs/0	NOD.Cg-Rag1^tm1Mom Tg(TcraAI4)1Dvs Tg(TcrbAI4)1Dvs/Dvs	MGI:3618788
cx71	Foxp3^tm1.1Ayr/Y Rag1^tm1Mom/Rag1^tm1Mom Tg(TcraTcrb)425Cbn/0	Not Specified	MGI:3574972

Genotype
MGI:3582287

hm1

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: B6.129S7-Rag1^tm1Mom

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

cardiovascular system

decreased vascular permeability ( J:78613 )

• after reperfusion mice do not have detectable IgM whereas wild-type have levels of 437 ug/ml

immune system

ear inflammation ( J:111828 )

increased eosinophil cell number ( J:111828 )

decreased immunoglobulin level ( J:111828 )

decreased IgM level ( J:78613 )

• upeon reperfusion of ischemic intestine, permeability index (PI) of injured Rag1-deficient mice is reduced compared to control treated wild-type (PI of 1.34 vs 3.26 in controls

• Rag1-deficient mice reconstituted with IgM show PI reduction similar to controls (PI of 2.86)

dermatitis ( J:111828 )

• after 16 days of MC903 treatment

hearing/vestibular/ear

ear inflammation ( J:111828 )

hematopoietic system

increased eosinophil cell number ( J:111828 )

decreased immunoglobulin level ( J:111828 )

decreased IgM level ( J:78613 )

• upeon reperfusion of ischemic intestine, permeability index (PI) of injured Rag1-deficient mice is reduced compared to control treated wild-type (PI of 1.34 vs 3.26 in controls

• Rag1-deficient mice reconstituted with IgM show PI reduction similar to controls (PI of 2.86)

integument

dermatitis ( J:111828 )

• after 16 days of MC903 treatment

mixed cellular infiltration to dermis ( J:111828 )

• MC903-treated ears showed a dermal infiltrate

epidermal hyperplasia ( J:111828 )

• MC903-treated ears display epidermal hyperplasia

scaly skin ( J:111828 )

• after 16 days of MC903 treatment

thick skin ( J:111828 )

• after 16 days of MC903 treatment

Genotype
MGI:7432330

hm2

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: B6.129S7-Rag1^tm1Mom/J

behavior/neurological

decreased anxiety-related response ( J:339075 )

• mice exposed to electronic foot shock for 8 days to induce anxiety do not exhibit reduced interest in the open-field test as is seen in wild-type mice, with no increase in thigmotaxis

• however, mice adoptively transferred with electronic foot shock-induced CD4+ T cells develop anxiety-like behavior in the open field test, while mice adoptively transferred with nontreated CD4+ T cells show weak anxiety-like symptoms

Genotype
MGI:7764756

hm3

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: C.129S7(B6)-Rag1^tm1Mom/Tvg

neoplasm

increased tumor incidence following infection ( J:329456 )

• Rauscher-like murine leukemia virus (RL-MuLV)-infected germ-free mutant mice show enhanced susceptibility to leukemia development, with about 85% (15/17) incidence of leukemia at 150 days compared to about 20% (13/71) in controls

• specific-pathogen free (SPF) mice exhibit increased RL-muLV-infection induced leukemia susceptibility compared with SPF controls

• however, both germ-free and specific-pathogen free mice show a similar frequency of infected splenocytes

Genotype
MGI:3850561

hm4

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129S7/SvEvBrd

immune system

abnormal thymus epithelium morphology ( J:125864 )

• medullary thymic epithelial cells that present self antigen are present in these mice

abnormal double-negative T cell morphology ( J:112990 )

• the number of CD44^-HSA⁺CD25^- DN thymyoctes is 2% of controls

• less proportion of these cells are actively cycling compared to controls

decreased inflammatory response ( J:94420 )

• intracolonic administration of the F2r (PAR-1) activating peptide, TFLLR, fails to induce inflammation in mutant colons as in wild-type mice

nervous system

abnormal neuron proliferation ( J:170591 )

• decrease in hippocampal neurogenesis

hematopoietic system

abnormal thymus epithelium morphology ( J:125864 )

• medullary thymic epithelial cells that present self antigen are present in these mice

abnormal double-negative T cell morphology ( J:112990 )

• the number of CD44^-HSA⁺CD25^- DN thymyoctes is 2% of controls

• less proportion of these cells are actively cycling compared to controls

cellular

abnormal neuron proliferation ( J:170591 )

• decrease in hippocampal neurogenesis

endocrine/exocrine glands

abnormal thymus epithelium morphology ( J:125864 )

• medullary thymic epithelial cells that present self antigen are present in these mice

Genotype
MGI:3818487

hm5

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/10

skeleton

skeleton phenotype ( J:129304 )

N • mice exhibit normal bone morphology

abnormal bone remodeling ( J:129304 )

• following ovariectamy, mice exhibit an increased bone loss compared to in similarly treated wild-type mice

Genotype
MGI:3767321

hm6

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

immune system

decreased susceptibility to induced colitis ( J:194587 )

• dextran sulfate sodium induced colitis is less severe than in wild-type controls

decreased neutrophil cell number ( J:119344 )

• 2 weeks or 1 month after infection with M. pulmonis, neutrophil numbers in the trachea are elevated above uninfected controls but are significantly lower than numbers in trachea of infected wild-type mice

abnormal lymphatic vessel morphology ( J:119344 )

• upon infection with Mycoplasma pulmonis, airway lymphatic vessel remodeling is largely absent from mutants, compared to significant invasion of region by lymphatic vessels in infected wild-type mice

autoimmune response ( J:138466 )

• antigen-specific autoimmunity developed after CD4-selected splenocytes from Tg(Tcra,Tcrb)9Rest donor mice

abnormal response to infection ( J:119344 )

• airway vascular and airway lymphatic vessel remodeling are impaired or absent compared to wild-type mice after M. pulmonis infection

hematopoietic system

decreased neutrophil cell number ( J:119344 )

• 2 weeks or 1 month after infection with M. pulmonis, neutrophil numbers in the trachea are elevated above uninfected controls but are significantly lower than numbers in trachea of infected wild-type mice

respiratory system

abnormal respiratory system morphology ( J:119344 )

• after 4 weeks, mice show impaired vascular remodeling of the airways in response to Mycoplasma pulmonis infection whereas wild-type show complex growth and reorganization ot the vascular beds

pigmentation

abnormal coat/hair pigmentation ( J:138466 )

• after transplant of CD4-selected splenocytes, mice develop extensive vitiligo

abnormal skin pigmentation ( J:138466 )

• after transplant of CD4-selected splenocytes, mice develop extensive vitiligo

vision/eye

abnormal eye morphology ( J:138466 )

• mice develop ocular injury with disruption of retinal architecture after transplant of CD4-selected splenocytes from Tg(Tcra,Tcrb)9Rest/Rag1^--mice

abnormal retina morphology ( J:138466 )

• mice develop ocular injury with disruption of retinal architecture after transplant of CD4-selected splenocytes from Tg(Tcra,Tcrb)9Rest/Rag1^--mice

integument

abnormal coat/hair pigmentation ( J:138466 )

• after transplant of CD4-selected splenocytes, mice develop extensive vitiligo

abnormal skin pigmentation ( J:138466 )

• after transplant of CD4-selected splenocytes, mice develop extensive vitiligo

digestive/alimentary system

decreased susceptibility to induced colitis ( J:194587 )

• dextran sulfate sodium induced colitis is less severe than in wild-type controls

Genotype
MGI:3687168

hm7

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD

hematopoietic system

small thymus ( J:111874 )

• nontransgenic Rag1 homozygotes have extremely small thymi

decreased lymphocyte cell number ( J:111874 )

• non-transgenic Rag1-null mice display lymphopenia more severe than transgenic Rag1-null mice

immune system

small thymus ( J:111874 )

• nontransgenic Rag1 homozygotes have extremely small thymi

decreased lymphocyte cell number ( J:111874 )

• non-transgenic Rag1-null mice display lymphopenia more severe than transgenic Rag1-null mice

endocrine/exocrine glands

small thymus ( J:111874 )

• nontransgenic Rag1 homozygotes have extremely small thymi

Genotype
MGI:2429492

hm8

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129S7/SvEvBrd * CD-1

immune system

thymus hypoplasia ( J:1934 )

• thymus contains 15 to 300 times fewer cells than wild-type or heterozygous controls

abnormal B cell differentiation ( J:1934 )

• spleen and bone marrow lack mature B cells; B cells are IgM and IgD negative, and only 1/4 to 1/3 are B220-positive

abnormal immunoglobulin V(D)J recombination ( J:1934 )

• absence of V(D)J recombination

absent mature B cells ( J:1934 )

• no mature B lymphocytes are observed in lymphoid organs

abnormal T cell morphology ( J:1934 )

• thymocytes are larger in 4-, 5-, and 7-week old mutants than in controls

• no mature T lymphocytes are seen in lymphoid organs

abnormal T cell differentiation ( J:1934 )

• thymocyte development is arrested at an early stage; cells are larger than normal, and are CD3^-, TCR alphabeta-negative, CD8^- CD4^-

abnormal T cell receptor V(D)J recombination ( J:1934 )

• absence of V(D)J recombination

spleen hypoplasia ( J:1934 )

• spleen contains 5 to 9 times fewer nonerythroid cells than wild-type or heterozygous controls

decreased IgM level ( J:1934 )

• no detectable IgM found in serum

abnormal inguinal lymph node morphology ( J:1934 )

• stroma-like structure found in inguinal lymph nodes location, with few, if any, nonerythroid cells recoverable from this structure

hematopoietic system

thymus hypoplasia ( J:1934 )

• thymus contains 15 to 300 times fewer cells than wild-type or heterozygous controls

abnormal B cell differentiation ( J:1934 )

• spleen and bone marrow lack mature B cells; B cells are IgM and IgD negative, and only 1/4 to 1/3 are B220-positive

abnormal immunoglobulin V(D)J recombination ( J:1934 )

• absence of V(D)J recombination

absent mature B cells ( J:1934 )

• no mature B lymphocytes are observed in lymphoid organs

abnormal T cell morphology ( J:1934 )

• thymocytes are larger in 4-, 5-, and 7-week old mutants than in controls

• no mature T lymphocytes are seen in lymphoid organs

abnormal T cell differentiation ( J:1934 )

• thymocyte development is arrested at an early stage; cells are larger than normal, and are CD3^-, TCR alphabeta-negative, CD8^- CD4^-

abnormal T cell receptor V(D)J recombination ( J:1934 )

• absence of V(D)J recombination

spleen hypoplasia ( J:1934 )

• spleen contains 5 to 9 times fewer nonerythroid cells than wild-type or heterozygous controls

decreased IgM level ( J:1934 )

• no detectable IgM found in serum

nervous system

nervous system phenotype ( J:1934 )

N • brain is normal in structure and size

behavior/neurological

behavior/neurological phenotype ( J:1934 )

N • normal activity, coordination and strength; normal nociception

endocrine/exocrine glands

thymus hypoplasia ( J:1934 )

• thymus contains 15 to 300 times fewer cells than wild-type or heterozygous controls

Genotype
MGI:3764009

hm9

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: NOD.129S7(B6)-Rag1^tm1Mom

immune system

increased immature B cell number ( J:109843 )

• IgLkappa- B220+ immature B cell numbers are increased as compared to NOD controls

increased granulocyte number ( J:109843 )

• numbers of granulocytes are increased in comparison to NOD controls

decreased mature B cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells

increased NK cell number ( J:109843 )

• numbers of NK cells are increased in comparison to NOD controls

decreased CD4-positive, alpha-beta T cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells

decreased CD8-positive, alpha-beta T cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells

increased macrophage cell number ( J:109843 )

• numbers of macrophages are increased in comparison to NOD controls

spleen hypoplasia ( J:109843 )

• nucleated spleen cells are reduced in 8-11 week old mice as compared to NOD control

decreased immunoglobulin level ( J:109843 )

• no serum immunoglobulin is detected in 218-334 day old mice

impaired natural killer cell mediated cytotoxicity ( J:109843 )

• Background Sensitivity: poly I:C stimulated spleen cells exhibit low levels of NK cell cyotoxic activity in comparison to C57BL/6 homozygotes

abnormal level of surface class II molecules ( J:109843 )

• four to five-fold decrease in cells expressing I-A^g7 as compared to NOD control

hematopoietic system

increased immature B cell number ( J:109843 )

• IgLkappa- B220+ immature B cell numbers are increased as compared to NOD controls

increased granulocyte number ( J:109843 )

• numbers of granulocytes are increased in comparison to NOD controls

decreased mature B cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells

increased NK cell number ( J:109843 )

• numbers of NK cells are increased in comparison to NOD controls

decreased CD4-positive, alpha-beta T cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells

decreased CD8-positive, alpha-beta T cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells

increased macrophage cell number ( J:109843 )

• numbers of macrophages are increased in comparison to NOD controls

spleen hypoplasia ( J:109843 )

• nucleated spleen cells are reduced in 8-11 week old mice as compared to NOD control

decreased immunoglobulin level ( J:109843 )

• no serum immunoglobulin is detected in 218-334 day old mice

impaired natural killer cell mediated cytotoxicity ( J:109843 )

• Background Sensitivity: poly I:C stimulated spleen cells exhibit low levels of NK cell cyotoxic activity in comparison to C57BL/6 homozygotes

Genotype
MGI:5558890

cn10

• Allelic Composition: Gt(ROSA)26Sor^tm1(DTA)Lky/?; Il5^{tm1.1(icre)Lky}/Il5⁺; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

immune system

abnormal immune system physiology ( J:206097 )

• no increase in type 2 innate lymphoid cells (ILC2) or induction of eotaxin-1 (Ccl11) is detected in lungs in response to administration of Il2 and Il33 in contrast to control mice lacking DTA expression which have a higher ILC2 population and Ccl11 expression

Genotype
MGI:3840971

cn11

• Allelic Composition: Foxo1^tm1Flv/Foxo1^tm1Flv; Rag1^tm1Mom/Rag1^tm1Mom; Tg(CD2-Il7r)1Asin/?; Tg(Cd4-cre)1Cwi/?; Tg(TcraTcrb)425Cbn/?
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * DBA/2

immune system

decreased T cell number ( J:147057 )

• the Il7r transgene rescues the low T cell numbers observed in mice with Foxo1-deficient OT-II T cells

hematopoietic system

decreased T cell number ( J:147057 )

• the Il7r transgene rescues the low T cell numbers observed in mice with Foxo1-deficient OT-II T cells

Genotype
MGI:3840970

cn12

• Allelic Composition: Foxo1^tm1Flv/Foxo1^tm1Flv; Rag1^tm1Mom/Rag1^tm1Mom; Tg(Cd4-cre)1Cwi/?; Tg(TcraTcrb)425Cbn/?
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * DBA/2

immune system

decreased T cell number ( J:147057 )

• T cell numbers in the spleen and lymph nodes are reduced 80-90% compared to Rag-null OT-II controls

hematopoietic system

decreased T cell number ( J:147057 )

• T cell numbers in the spleen and lymph nodes are reduced 80-90% compared to Rag-null OT-II controls

Genotype
MGI:5552953

cn13

• Allelic Composition: Pdpn^tm2.1Mlkn/Pdpn^tm2.1Mlkn; Rag1^tm1Mom/Rag1^tm1Mom; Tg(Pdgfrb-cre)9Rha/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

immune system

absent lymphocyte ( J:205423 )

cardiovascular system

cardiovascular system phenotype ( J:205423 )

N • mice do not exhibit bleeding into mucosal lymph nodes unlike in Pdpn^tm2.1Mlkn/Pdpn^tm2.1Mlkn Tg(Pdgfrb-cre)9Rha mice

hematopoietic system

absent lymphocyte ( J:205423 )

Genotype
MGI:3850056

cn14

• Allelic Composition: Nlrp3^tm1Hhf/Nlrp3⁺; Rag1^tm1Mom/Rag1^tm1Mom; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:150054 )

• mice die between 2 and 14 days after birth probably due to multisystem organ failure secondary to inflammation and necrosis

• 70% of mice die between 7-14 days

• absence of B and T cells demonstrates disease is not caused by the adaptive immune system

growth/size/body

slow postnatal weight gain ( J:150054 )

• mutant pups gained weight slowly, and then lost weight before dying

immune system

absent B cells ( J:150054 )

absent T cells ( J:150054 )

hematopoietic system

absent B cells ( J:150054 )

absent T cells ( J:150054 )

integument

reddish skin ( J:150054 )

• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4

scaly skin ( J:150054 )

• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4

Genotype
MGI:7659107

cn15

• Allelic Composition: Ctps1^{tm1c(KOMP)Wtsi}/Ctps1^{tm1c(KOMP)Wtsi}; Tg(Cd4-cre)1Cwi/0; Foxp3^sf/Y; Rag1^tm1Mom/Rag1⁺
• Genetic Background: mixed

growth/size/body

decreased body weight ( J:348981 )

♂ • weight does not reach control levels at 40-50 days and 60-75 days

enlarged spleen ( J:348981 )

♂ • by day 44, mice develop enlarged spleen

endocrine/exocrine glands

thymus hypoplasia ( J:348981 )

• by day 44, thymus has reduced cellularity

immune system

decreased T cell proliferation ( J:348981 )

♂ • both CD8+ and CD4+ T cells show a reduced capacity to expand in response to CD3/CD28 stimulation

thymus hypoplasia ( J:348981 )

• by day 44, thymus has reduced cellularity

enlarged spleen ( J:348981 )

♂ • by day 44, mice develop enlarged spleen

decreased regulatory T cell number ( J:348981 )

♂ • mice exhibit a deficiency in T regulatory cells (CD4+, CD25+, FoxP3+)

decreased inflammatory response ( J:348981 )

♂ • mice show prevention of the fatal systemic autoimmune and inflammatory disease that is seen in Foxp3^sf/Y mice, with mice surviving at least up to 80 days and no presentation of scaly tails and ears, and no inflammation and tissue disruption at day 44

♂ • values of total T cells return to normal and the accumulation of effector memory CD4+ and CD8+ T cells in the spleen that is seen in single Foxp3/Y mice is reduced

hematopoietic system

decreased T cell proliferation ( J:348981 )

♂ • both CD8+ and CD4+ T cells show a reduced capacity to expand in response to CD3/CD28 stimulation

thymus hypoplasia ( J:348981 )

• by day 44, thymus has reduced cellularity

enlarged spleen ( J:348981 )

♂ • by day 44, mice develop enlarged spleen

decreased regulatory T cell number ( J:348981 )

♂ • mice exhibit a deficiency in T regulatory cells (CD4+, CD25+, FoxP3+)

cellular

decreased T cell proliferation ( J:348981 )

♂ • both CD8+ and CD4+ T cells show a reduced capacity to expand in response to CD3/CD28 stimulation

Genotype
MGI:3850631

cx16

• Allelic Composition: Man2a1^tm1Jxm/Man2a1^tm1Jxm; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: B6.129-Rag1^tm1Mom Man2a1^tm1Jxm

growth/size/body

weight loss ( J:124348 )

• severe weight loss

renal/urinary system

increased mesangial cell apoptosis ( J:124348 )

• increased mesangial cell apoptosis between 6 and 9 months of age

increased urine protein level ( J:124348 )

• increased proteinuria

kidney inflammation ( J:124348 )

• exacerbated kidney disease

• increased macrophage infiltration of the kidney

abnormal nephron morphology ( J:124348 )

• nephron loss

• increased tissue sclerosis

immune system

kidney inflammation ( J:124348 )

• exacerbated kidney disease

• increased macrophage infiltration of the kidney

homeostasis/metabolism

increased urine protein level ( J:124348 )

• increased proteinuria

integument

alopecia ( J:124348 )

cellular

increased mesangial cell apoptosis ( J:124348 )

• increased mesangial cell apoptosis between 6 and 9 months of age

Genotype
MGI:4947955

cx17

• Allelic Composition: Mpz^tm1Msch/Mpz⁺; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: B6.129S7-Mpz^tm1Msch Rag1^tm1Mom

nervous system

increased Schwann cell number ( J:59319 )

• increase in the number of Schwann cells around the quadriceps femoral nerves at 13 months of age is less than that in age matched mutant mice heterozygous for the Rag1 null allele

abnormal neuron morphology ( J:59319 )

• pathological lesions indicative of compromised myelin maintenance in the quadriceps femoral nerves at 13 months of age are less severe than those in age matched mutant mice heterozygous for the Rag1 null allele

abnormal myelin sheath morphology ( J:59319 )

• myelin sheaths of quadriceps femoral nerves at 13 months of age are thicker than those in age matched mutant mice heterozygous for the Rag1 null allele

abnormal myelination ( J:59319 )

• myelin degeneration in the quadriceps femoral nerves at 13 months of age is less severe than in age matched mutant mice heterozygous for the Rag1 null allele

abnormal nerve conduction ( J:59319 )

• impaired conduction with prolonged latencies of M-responses and of F waves after distal or proximal stimulations

• impairment is less severe than in mutant mice heterozygous for the Rag1 null allele

immune system

absent CD4-positive, alpha-beta T cells ( J:59319 )

absent CD8-positive, alpha-beta T cells ( J:59319 )

hematopoietic system

absent CD4-positive, alpha-beta T cells ( J:59319 )

absent CD8-positive, alpha-beta T cells ( J:59319 )

Genotype
MGI:5702315

cx18

• Allelic Composition: Cd160^tm1Yxf/Cd160^tm1Yxf; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: B6.Cg-Rag1^tm1Mom Cd160^tm1Yxf

immune system

decreased interferon-gamma secretion ( J:222131 )

• reduced interferon gamma production from splenocytes stimulated by Nk1.1 cross-linking

neoplasm

increased tumor growth/size ( J:222131 )

• increased tumor volume/weight following inoculation with NK-dependent B16 or RMA-S (no MHC class I surface expression) tumor cells as compared to homozygous Rag^tm1Mom control

• tumors generated by inoculation with RMA (normal MHC class I) cells have weights similar to Rag^tm1Mom controls

Genotype
MGI:7262906

cx19

• Allelic Composition: Clec2h^tm1.1Apma/Clec2h^tm1.1Apma; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: B6.Cg-Rag1^tm1Mom Clec2h^tm1.1Apma

renal/urinary system

abnormal kidney capillary morphology ( J:322835 )

• kidneys show an increase in endocapillary proliferation

kidney inflammation ( J:322835 )

• kidneys show increased presence of IL-12 and IFN-gamma

• kidneys exhibit an extensive periglomerular accumulation of CD45+ cells, consisting of CD11c+, F4/80+, and Nkp46+ cells, indicating inflammation

abnormal renal glomerulus morphology ( J:322835 )

• glomerular lesions indicative of mild proliferative glomerulopathy and areas of glomerular fibrosis

increased mesangial cell number ( J:322835 )

• an increase in the presence of mesangial cellularity

glomerulosclerosis ( J:322835 )

• glomerulosclerosis or focal segmental sclerosis

glomerular crescent ( J:322835 )

renal glomerulus fibrosis ( J:322835 )

• areas of glomerular fibrosis

renal interstitial fibrosis ( J:322835 )

renal tubule atrophy ( J:322835 )

adipose tissue

abnormal adipose tissue amount ( J:322835 )

• abdominal lipid weight is increased compared to that in single Rag1 mutant homozygotes, but to a lesser extent than in single Clec2h mutant homozygotes

cardiovascular system

abnormal kidney capillary morphology ( J:322835 )

• kidneys show an increase in endocapillary proliferation

growth/size/body

decreased body weight ( J:322835 )

• body weight is lower than in single Rag1 mutant homozygotes

immune system

kidney inflammation ( J:322835 )

• kidneys show increased presence of IL-12 and IFN-gamma

• kidneys exhibit an extensive periglomerular accumulation of CD45+ cells, consisting of CD11c+, F4/80+, and Nkp46+ cells, indicating inflammation

cellular

increased mesangial cell number ( J:322835 )

• an increase in the presence of mesangial cellularity

Genotype
MGI:3845009

cx20

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tg(Tcra,Tcrb)HRCAll/0
• Genetic Background: B6.Cg-Rag1^tm1Mom Tg(Tcra,Tcrb)HRCAll

immune system

abnormal T cell differentiation ( J:131347 )

• mature peripheral T cells are selected to the CD8+ lineage

• however, mice do not exhibit clonal deletion or co-receptor downregulation in the thymus or activation in the periphery

abnormal T cell subpopulation ratio ( J:131347 )

• mature peripheral T cells are selected to the CD8+ lineage

absent CD4-positive, alpha-beta T cells ( J:131347 )

increased CD8-positive, alpha-beta T cell number ( J:131347 )

hematopoietic system

abnormal T cell differentiation ( J:131347 )

• mature peripheral T cells are selected to the CD8+ lineage

• however, mice do not exhibit clonal deletion or co-receptor downregulation in the thymus or activation in the periphery

abnormal T cell subpopulation ratio ( J:131347 )

• mature peripheral T cells are selected to the CD8+ lineage

absent CD4-positive, alpha-beta T cells ( J:131347 )

increased CD8-positive, alpha-beta T cell number ( J:131347 )

Genotype
MGI:6305814

cx21

• Allelic Composition: H2^u/H2^u; Rag1^tm1Mom/Rag1^tm1Mom; Tg(Tcra19,Tcrb19)#Stl/0
• Genetic Background: either: (involves: 129S7/SvEvBrd * C57BL/6 * PL/J) or (involves: 129S7/SvEvBrd * C57BL/6 * C57BL/10 * PL/J)

immune system

increased susceptibility to autoimmune disorder ( J:19795 )

• 100% of mice develop spontaneous autoimmune encephalomyelitis within 12 months

• onset and rate of progression of disease varies, with an average age of onset of 13 weeks

• cerebellum and spinal cord exhibit patchy lesions with mononuclear cell infiltrates

• activated myelin basic protein (MBP)-specific T cells are found in the brain but not in the peripheral lymphoid tissues

behavior/neurological

limb paralysis ( J:19795 )

• weakness or paralysis of the hind legs is seen first and then extends to the front legs

• once hind legs are completely paralyzed, the disease progresses very rapidly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
multiple sclerosis		DOID:2377	OMIM:612594 OMIM:612595 OMIM:612596	J:19795

Genotype
MGI:3826833

cx22

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tyrp1^B-w/Tyrp1^B-w; X/Tg(Tcra,Tcrb)9Rest
• Genetic Background: involves: 101/Rl * 129S7/SvEvBrd * C3H/Rl * C57BL/6

neoplasm

abnormal tumor susceptibility ( J:138466 )

♂ • inoculation with B16 melanoma cells results in 100% tumor take in transgenic mice; tumor growth is only minimally delayed compared to non-transgenic control mice

Genotype
MGI:6452104

cx23

• Allelic Composition: Pld4^tm1.2Nemz/Pld4^tm1.2Nemz; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129 * 129S7/SvEvBrd * C57BL/6J * FVB/N

hematopoietic system

decreased NK T cell number ( J:281205 )

abnormal peritoneal macrophage morphology ( J:281205 )

• elevated expression of major histocompatibility complex (MHC) class II peptides on surface of resident peritoneal macrophages

immune system

decreased NK T cell number ( J:281205 )

abnormal peritoneal macrophage morphology ( J:281205 )

• elevated expression of major histocompatibility complex (MHC) class II peptides on surface of resident peritoneal macrophages

Genotype
MGI:4354514

cx24

• Allelic Composition: Itk^tm1Ljb/Itk^tm1Ljb; Rag1^tm1Mom/Rag1^tm1Mom; Tg(Tcra5CC7,Tcrb5CC7)IWep/?
• Genetic Background: involves: 129 * C57BL/10

immune system

abnormal CD4-positive T cell differentiation ( J:93606 )

• when stimulated with low concentrations of antigen, CD4 T cells differentiate predominately into a Th1 phenotype while controls develop into a Th2 phenotype

• these T cells have increased expression of the T-bet transcription factor

decreased interferon-gamma secretion ( J:93606 )

• T cells cultured under Th1 polarizing conditions produce less IFN-gamma than controls

• Th1 T cells produce 1.5- to 200-fold less IFN-gamma than controls

decreased interleukin-10 secretion ( J:93606 )

• T cells cultured under Th2 polarizing conditions produce less IL-10 than controls

decreased interleukin-4 secretion ( J:93606 )

• T cells cultured under Th2 polarizing conditions produce less IL-4 than controls

• Th2 T cells produce 3.5- to 300-fold less IL-4 than controls

decreased interleukin-5 secretion ( J:93606 )

• T cells cultured under Th2 polarizing conditions produce less IL-5 than controls

hematopoietic system

abnormal CD4-positive T cell differentiation ( J:93606 )

• when stimulated with low concentrations of antigen, CD4 T cells differentiate predominately into a Th1 phenotype while controls develop into a Th2 phenotype

• these T cells have increased expression of the T-bet transcription factor

Genotype
MGI:3812196

cx25

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Slc46a2^tm1Moki/Slc46a2⁺; Tg(TcraB12,TcrbB12)1Rest/0
• Genetic Background: involves: 129 * C57BL/6

immune system

increased T cell apoptosis ( J:140121 )

• massive cell death of double negative as well as CD4⁺ and/or CD8⁺ thymocytes occur in these mice

thymus hypoplasia ( J:140121 )

• thymic cellularity is reduced by about 5-fold compared to transgenic Rag1 null mice

decreased double-positive T cell number ( J:140121 )

• double-positive T cells are absent in the thymus

arrested T cell differentiation ( J:140121 )

• T cells are arrested in the DN3 stage

hematopoietic system

increased T cell apoptosis ( J:140121 )

• massive cell death of double negative as well as CD4⁺ and/or CD8⁺ thymocytes occur in these mice

thymus hypoplasia ( J:140121 )

• thymic cellularity is reduced by about 5-fold compared to transgenic Rag1 null mice

decreased double-positive T cell number ( J:140121 )

• double-positive T cells are absent in the thymus

arrested T cell differentiation ( J:140121 )

• T cells are arrested in the DN3 stage

cellular

increased T cell apoptosis ( J:140121 )

• massive cell death of double negative as well as CD4⁺ and/or CD8⁺ thymocytes occur in these mice

endocrine/exocrine glands

thymus hypoplasia ( J:140121 )

• thymic cellularity is reduced by about 5-fold compared to transgenic Rag1 null mice

Genotype
MGI:5550271

cx26

• Allelic Composition: Ndfip1^{Gt(RRD002)Byg}/Ndfip1^{Gt(RRD002)Byg}; Rag1^tm1Mom/Rag1^tm1Mom; Tg(TcraTcrb)425Cbn/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * BALB/c * C57BL/6

immune system

immune system phenotype ( J:205692 )

N • unlike Ndfip1^{Gt(RRD002)Byg} homozygotes, mice do not develop eosinophilic inflammation and T cells do not acquire an activated phenotype in the absence of antigen

Genotype
MGI:3698843

cx27

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tnfrsf25^tm1Mjo/Tnfrsf25^tm1Mjo
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

hematopoietic system

abnormal T cell differentiation ( J:84536 )

• thymocyte development is arrested at the CD25+CD44- double negative (DN) stage

immune system

abnormal T cell differentiation ( J:84536 )

• thymocyte development is arrested at the CD25+CD44- double negative (DN) stage

Genotype
MGI:7277703

cx28

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tnfsf14^tm1Kpf/Tnfsf14^tm1Kpf
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

skeleton

decreased osteoclast cell number ( J:294030 )

increased osteoblast cell number ( J:294030 )

• slight increase

abnormal trabecular bone morphology ( J:294030 )

• increase in cancellous bone structure in comparison to mice null for Rag alone

hematopoietic system

decreased osteoclast cell number ( J:294030 )

immune system

decreased osteoclast cell number ( J:294030 )

Genotype
MGI:3818486

cx29

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/10

skeleton

increased bone trabecula number ( J:129304 )

• the number of trabeculae are increased compared to wild-type mice

• however, trabecular thickness is normal

increased trabecular bone connectivity density ( J:129304 )

• the space between trabeculae is reduced compared to in wild-type mice

increased bone mass ( J:129304 )

• bone mass is increased 30% compared to in Tyrobp^tm1.1Viv homozygotes and 60% compared to in wild-type mice and Rag1^tm1Mom homozygotes

osteopetrosis ( J:129304 )

• severe

abnormal bone remodeling ( J:129304 )

• following ovariectamy, mice exhibit an increased bone loss compared to in similarly treated wild-type mice or Tyrobp^tm1.1Viv homozygotes

abnormal osteoclast physiology ( J:129304 )

• collagen type I degradation products are decreased 17% compared to in wild-type mice

immune system

abnormal osteoclast physiology ( J:129304 )

• collagen type I degradation products are decreased 17% compared to in wild-type mice

hematopoietic system

abnormal osteoclast physiology ( J:129304 )

• collagen type I degradation products are decreased 17% compared to in wild-type mice

Genotype
MGI:4940117

cx30

• Allelic Composition: Ctla4^tm1All/Ctla4^tm1All; Rag1^tm1Mom/Rag1^tm1Mom; Tg(TcraTcrb)8Rest/0
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6

mortality/aging

mortality/aging ( J:140448 )

N • mice exhibit a normal lifespan

immune system

immune system phenotype ( J:140448 )

N • CD8+ T cells exhibit a completely naive phenotype

pigmentation

pigmentation phenotype ( J:140448 )

N • mice do not develop autoimmune vitiligo

Genotype
MGI:5635503

cx31

• Allelic Composition: H2^dlAb1-Ea/H2^dlAb1-Ea; Rag1^tm1Mom/Rag1^tm1Mom; Tg(HLA-DRA,HLA-DRB5*0101)loKito/0; Tg(TRATL3A6,TRBTL3A6)#Kito/0
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

immune system

brain inflammation ( J:189816 )

• mice develop spontaneous experimental autoimmune encephalitis with an incidence of 5%; onset of disease is around 12 weeks of age

nervous system

brain inflammation ( J:189816 )

• mice develop spontaneous experimental autoimmune encephalitis with an incidence of 5%; onset of disease is around 12 weeks of age

Genotype
MGI:5635499

cx32

• Allelic Composition: H2^dlAb1-Ea/H2^dlAb1-Ea; Rag1^tm1Mom/Rag1^tm1Mom; Tg(HLA-DRA,HLA-DRB5*0101)hiKito/0; Tg(TRATL3A6,TRBTL3A6)#Kito/0
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

immune system

brain inflammation ( J:189816 )

• mice develop spontaneous autoimmune encephalitis with an incidence of 58.3; onset of disease is around 6 weeks of age

nervous system

brain inflammation ( J:189816 )

• mice develop spontaneous autoimmune encephalitis with an incidence of 58.3; onset of disease is around 6 weeks of age

Genotype
MGI:4360345

cx33

• Allelic Composition: Lck^tm1Mak/Lck^tm1Mak; Rag1^tm1Mom/Rag1⁺; Tg(Lck-Fyn*Y528F)5525Cjg/0
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

hematopoietic system

abnormal T cell differentiation ( J:37062 )

• the transgene partially rescues arrest of T cell development associated with Lck deficiency

• thymocyte numbers are normal

• splenic gamma-delta T cell numbers are normal

• expression of TCR and CD5 on transitional single-positive thymocytes is slightly lower than controls

decreased T cell number ( J:37062 )

• alpha beta T cell numbers are less than half of wild-type controls

immune system

abnormal T cell differentiation ( J:37062 )

• the transgene partially rescues arrest of T cell development associated with Lck deficiency

• thymocyte numbers are normal

• splenic gamma-delta T cell numbers are normal

• expression of TCR and CD5 on transitional single-positive thymocytes is slightly lower than controls

decreased T cell number ( J:37062 )

• alpha beta T cell numbers are less than half of wild-type controls

Genotype
MGI:3687167

cx34

• Allelic Composition: H2^g7/H2^g7; Ins2^tm1Jja/Ins2^tm1Jja; Rag1^tm1Mom/Rag1^tm1Mom; Tg(TcraBDC12-4.1)10Jos/0; Tg(TcrbBDC12-4.1)82Gse/0
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6 * FVB * NOD

homeostasis/metabolism

increased circulating glucose level ( J:111874 )

immune system

increased susceptibility to autoimmune diabetes ( J:111874 )

• mice develop diabetes (blood glucose >250 ml/dl) more rapidly than transgenic Rag1-null, Ins2-sufficient mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:111874

Genotype
MGI:3769348

cx35

• Allelic Composition: Jak3^tm1Ljb/Jak3^tm1Ljb; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd

immune system

immune system phenotype ( J:56629 )

N • unlike Jak3 null mice that are wild-type for Rag1, no splenomegaly is seen

abnormal splenic cell ratio ( J:56629 )

• FACs profile of spleens resemble those of mice homozygous null for Rag1 alone

hematopoietic system

abnormal splenic cell ratio ( J:56629 )

• FACs profile of spleens resemble those of mice homozygous null for Rag1 alone

Genotype
MGI:3699096

cx36

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * BALB/cJ * C57BL/6J

skeleton

abnormal osteoclast differentiation ( J:117880 )

• no change in abnormal osteoclast formation compared to mice homozygous for the Sh3bp2 allele alone

decreased bone mineral density ( J:117880 )

• decreased bone mineral density in the long bones at 10 weeks of age

• no improvement in bone loss compared to mice homozygous for the Sh3bp2 allele alone

immune system

abnormal osteoclast differentiation ( J:117880 )

• no change in abnormal osteoclast formation compared to mice homozygous for the Sh3bp2 allele alone

increased circulating tumor necrosis factor level ( J:117880 )

• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone

increased inflammatory response ( J:117880 )

• mice still develop the macrophage-rich inflammatory infiltrates in internal organs and periosteal regions that are seen in mice homozygous for the Sh3bp2 allele alone

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:117880 )

• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone

hematopoietic system

abnormal osteoclast differentiation ( J:117880 )

• no change in abnormal osteoclast formation compared to mice homozygous for the Sh3bp2 allele alone

cellular

abnormal osteoclast differentiation ( J:117880 )

• no change in abnormal osteoclast formation compared to mice homozygous for the Sh3bp2 allele alone

Genotype
MGI:5555860

cx37

• Allelic Composition: Col1a1^{tm1(tetO-Fos)Wag}/Col1a1⁺; Rag1^tm1Mom/Rag1^tm1Mom; Tg(KRT5-rtTA)T2D6Sgkd/0
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6 * FVB/N

integument

integument phenotype ( J:201145 )

N • doxycycline-treated mice exhibit normal keratinocyte proliferation and activation

skin lesions ( J:201145 )

• in doxycycline-treated mice but smaller than in mice with wild-type Rag1

skin hyperplasia ( J:201145 )

• in doxycycline-treated mice but less so than in mice with wild-type Rag1

Genotype
MGI:5007931

cx38

• Allelic Composition: Mefv^{tm5.1(MEFV)Chae}/Mefv^{tm5.1(MEFV)Chae}; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6

immune system

increased circulating interleukin-1 beta level ( J:172117 )

increased circulating interleukin-6 level ( J:172117 )

increased circulating tumor necrosis factor level ( J:172117 )

abnormal cytokine secretion ( J:172117 )

• activated T cells secrete less cytokines than in activated T cells from Mefv^{tm5.1(MEFV)Chae} homozygotes but more cytokines than in actiavted T cells from wild-type

• activated T cells exhibit increased secretion of IL1b, IL2, IL4, IL5, IL9, IL10, IL12b, IL12, IL13, IL17, IFN-gamma, RANTES, G-CSF, MIP1alpha, KC, GM-CSF, MCP-1, and MIP1beta compared with activated T cells from wild-type mice

increased interferon-gamma secretion ( J:172117 )

• in activated T cells

increased interleukin-1 beta secretion ( J:172117 )

• in activated T cells

increased interleukin-10 secretion ( J:172117 )

• in activated T cells

increased interleukin-12 secretion ( J:172117 )

• in activated T cells

increased interleukin-13 secretion ( J:172117 )

• in activated T cells

increased interleukin-17 secretion ( J:172117 )

• in activated T cells

increased interleukin-2 secretion ( J:172117 )

• in activated T cells

increased interleukin-4 secretion ( J:172117 )

• in activated T cells

increased interleukin-5 secretion ( J:172117 )

• in activated T cells

increased interleukin-9 secretion ( J:172117 )

• in activated T cells

increased inflammatory response ( J:172117 )

• mice exhibit inflammatory phenotypes observed in Mefv^{tm5.1(MEFV)Chae} homozygotes

growth/size/body

decreased body weight ( J:172117 )

homeostasis/metabolism

increased circulating interleukin-1 beta level ( J:172117 )

increased circulating interleukin-6 level ( J:172117 )

increased circulating tumor necrosis factor level ( J:172117 )

Genotype
MGI:5576255

cx39

• Allelic Composition: Nfil3^tm1Pbro/Nfil3^tm1Pbro; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6

immune system

immune system phenotype ( J:209365 )

N • mice do not develop colitis

Genotype
MGI:5433362

cx40

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Rasa3^scat/Rasa3^scat
• Genetic Background: involves: 129S7/SvEvBrd * BALB/cBy

hematopoietic system

abnormal hematopoietic system morphology/development ( J:186485 )

• mice exhibit the same phenotype as Rasa3^scat homozygotes

immune system

abnormal immune system morphology ( J:186485 )

• mice exhibit the same phenotype as Rasa3^scat homozygotes

Genotype
MGI:3578558

cx41

• Allelic Composition: Plcg2^Ali5/Plcg2⁺; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129S7/SvEvBrd * C3HeB/FeJ * C3HeB/FeJ-Plcg2^Ali5

immune system

chronic inflammation ( J:97930 )

• approximately 70% of homozygous mice developed despite absence of B and T cells

osteoarthritis ( J:97930 )

• resulting in severe arthritis of the small joints of the paws and missing phalanges

dermatitis ( J:97930 )

• in the superficial layers of the skin of the paws and ears

skeleton

osteoarthritis ( J:97930 )

• resulting in severe arthritis of the small joints of the paws and missing phalanges

integument

dermatitis ( J:97930 )

• in the superficial layers of the skin of the paws and ears

Genotype
MGI:3760618

cx42

• Allelic Composition: Pstpip2^Lupo/Pstpip2^Lupo; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129S7/SvEvBrd * C3HeB/FeJ * C57BL/6J

immune system

skin inflammation ( J:125785 )

• 88% of mice develop skin inflammation with a mean age of onset of 43+/-9 days compared to 98% (42.2+/-4 days) on a C3H background and 52% (124+/-92 days) on a C3H C57BL/6 background

• paw inflammation develops and is worse than in Pstpip2^Lupo homozygotes on a C3H C57BL/6 background

integument

skin inflammation ( J:125785 )

• 88% of mice develop skin inflammation with a mean age of onset of 43+/-9 days compared to 98% (42.2+/-4 days) on a C3H background and 52% (124+/-92 days) on a C3H C57BL/6 background

• paw inflammation develops and is worse than in Pstpip2^Lupo homozygotes on a C3H C57BL/6 background

Genotype
MGI:3803975

cx43

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tg(Lck-Akt1*E40K)E-3Pnt/0
• Genetic Background: involves: 129S7/SvEvBrd * C3H/He * C57BL/6

immune system

increased thymocyte number ( J:135903 )

• thymocyte numbers increase with age

increased double-positive T cell number ( J:135903 )

• 96% of thymocytes are double positive

• the presence of the transgene rescues the block of T cell development that occurs at DN3 in Rag1^tm1Mom homozygotes

hematopoietic system

increased thymocyte number ( J:135903 )

• thymocyte numbers increase with age

increased double-positive T cell number ( J:135903 )

• 96% of thymocytes are double positive

• the presence of the transgene rescues the block of T cell development that occurs at DN3 in Rag1^tm1Mom homozygotes

endocrine/exocrine glands

increased thymocyte number ( J:135903 )

• thymocyte numbers increase with age

Genotype
MGI:3818750

cx44

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Xrcc5^tm1Dbr/Xrcc5^tm1Dbr
• Genetic Background: involves: 129S7/SvEvBrd * C57BL

nervous system

increased cerebellar granule cell number ( J:141515 )

• mice exhibit a focal increase in external granule cells compared to in wild-type mice

neoplasm

neoplasm ( J:141515 )

N • despite the increase in granule cells, mice do not develop medulloblastoma

Genotype
MGI:3818749

cx45

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Trp53^tm1Brd/Trp53^tm1Brd
• Genetic Background: involves: 129S7/SvEvBrd * C57BL

mortality/aging

premature death ( J:141515 )

• all mice die by 45 weeks of age

neoplasm

increased pituitary adenoma incidence ( J:141515 )

• in one mouse

increased T cell derived lymphoma incidence ( J:141515 )

• 53% mice develop T cell lymphomas

increased hepatocellular carcinoma incidence ( J:141515 )

• in one mouse

increased medulloblastoma incidence ( J:141515 )

• mice that exhibit vertigo develop medulloblastoma

• 8.1% of mice exhibit medulloblastoma at the time of morbidity

increased sarcoma incidence ( J:141515 )

• in one mouse

increased hemangiosarcoma incidence ( J:141515 )

• in one mouse

respiratory system

respiratory distress ( J:141515 )

• in two-thirds of mice

behavior/neurological

impaired balance ( J:141515 )

• one mouse exhibited an acute onset of vertigo that led to disabled mobility and severe dehydration as a result of inability to reach the water source

homeostasis/metabolism

dehydration ( J:141515 )

• one mouse exhibited an acute onset of vertigo that led to disabled mobility and severe dehydration as a result of inability to reach the water source

nervous system

increased pituitary adenoma incidence ( J:141515 )

• in one mouse

increased medulloblastoma incidence ( J:141515 )

• mice that exhibit vertigo develop medulloblastoma

• 8.1% of mice exhibit medulloblastoma at the time of morbidity

endocrine/exocrine glands

increased pituitary adenoma incidence ( J:141515 )

• in one mouse

increased T cell derived lymphoma incidence ( J:141515 )

• 53% mice develop T cell lymphomas

liver/biliary system

increased hepatocellular carcinoma incidence ( J:141515 )

• in one mouse

hematopoietic system

increased T cell derived lymphoma incidence ( J:141515 )

• 53% mice develop T cell lymphomas

immune system

increased T cell derived lymphoma incidence ( J:141515 )

• 53% mice develop T cell lymphomas

Genotype
MGI:3818748

cx46

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Trp53^tm1Brd/Trp53^tm1Brd; Xrcc5^tm1Dbr/Xrcc5^tm1Dbr
• Genetic Background: involves: 129S7/SvEvBrd * C57BL

mortality/aging

premature death ( J:141515 )

• median lifespan is 14 weeks compared to 7 weeks in Trp53^tm1Brd Xrcc5^tm1Dbr

• maximum lifespan is 20 weeks compared to 16 weeks in Trp53^tm1Brd Xrcc5^tm1Dbr

neoplasm

increased stomach tumor incidence ( J:141515 )

• one mouse developed a stomach neoplasm

increased T cell derived lymphoma incidence ( J:141515 )

• 55% mice develop T cell lymphomas in the liver, spleen, lymph nodes, bone marrow, kidney, heart, lungs and ovaries

increased medulloblastoma incidence ( J:141515 )

• mice that exhibit vertigo develop medulloblastoma

• 66.7% of mice exhibit medulloblastoma at the time of morbidity

increased sarcoma incidence ( J:141515 )

• in one mouse

respiratory system

respiratory distress ( J:141515 )

• one-fifth of mice exhibit labored breathing prior to death compared to two-thirds of Rag1^tm1Mom Trp53^tm1Brd

behavior/neurological

impaired balance ( J:141515 )

• two-thirds of mice exhibit an acute onset of vertigo that leads to disabled mobility and severe dehydration as a result of inability to reach the water source

homeostasis/metabolism

dehydration ( J:141515 )

• two-thirds of mice exhibit an acute onset of vertigo that leads to disabled mobility and severe dehydration as a result of inability to reach the water source

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:141515 )

• 55% mice develop T cell lymphomas in the liver, spleen, lymph nodes, bone marrow, kidney, heart, lungs and ovaries

nervous system

increased medulloblastoma incidence ( J:141515 )

• mice that exhibit vertigo develop medulloblastoma

• 66.7% of mice exhibit medulloblastoma at the time of morbidity

digestive/alimentary system

increased stomach tumor incidence ( J:141515 )

• one mouse developed a stomach neoplasm

immune system

increased T cell derived lymphoma incidence ( J:141515 )

• 55% mice develop T cell lymphomas in the liver, spleen, lymph nodes, bone marrow, kidney, heart, lungs and ovaries

hematopoietic system

increased T cell derived lymphoma incidence ( J:141515 )

• 55% mice develop T cell lymphomas in the liver, spleen, lymph nodes, bone marrow, kidney, heart, lungs and ovaries

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:141515

Genotype
MGI:5512886

cx47

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tg(CAG-Lyn*)#Paau/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

immune system

decreased inflammatory response ( J:151886 )

• skin inflammatory disease is improved compared to single Tg(CAG-Lyn*)#Paau transgenic mice

Genotype
MGI:5474627

cx48

• Allelic Composition: Ier3^tm1Mxw/Ier3^tm1Mxw; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

digestive/alimentary system

decreased susceptibility to induced colitis ( J:194587 )

• dextran sulfate sodium induced colitis is more severe than in either single homozygote but less severe than in wild-type controls

immune system

decreased susceptibility to induced colitis ( J:194587 )

• dextran sulfate sodium induced colitis is more severe than in either single homozygote but less severe than in wild-type controls

Genotype
MGI:6305871

cx49

• Allelic Composition: H2^b/H2^b; Rag1^tm1Mom/Rag1^tm1Mom; Tg(Tcra19,Tcrb19)#Stl/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

immune system

immune system phenotype ( J:19795 )

N • mice do not show signs of spontaneous autoimmune encephalomyelitis within 12 months and do not develop experimental autoimmune encephalomyelitis after immunization with myelin basic protein (MBP)

Genotype
MGI:2665134

cx50

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tg(LPV-TAg1135)11Tvd/0; Tg(TcrLCMV)327Sdz/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * DBA/2

mortality/aging

premature death ( J:47667 )

• survival time at which half of the mutants are sacrificed or die due to illness is 101 days

neoplasm

increased T cell derived lymphoma incidence ( J:47667 )

• 100% of mutants develop thymic lymphoma within the same accelerated time frame as mutants heterozygous for Rag1 and hemizygous for the two transgenes

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:47667 )

• 100% of mutants develop thymic lymphoma within the same accelerated time frame as mutants heterozygous for Rag1 and hemizygous for the two transgenes

hematopoietic system

increased T cell derived lymphoma incidence ( J:47667 )

• 100% of mutants develop thymic lymphoma within the same accelerated time frame as mutants heterozygous for Rag1 and hemizygous for the two transgenes

immune system

increased T cell derived lymphoma incidence ( J:47667 )

• 100% of mutants develop thymic lymphoma within the same accelerated time frame as mutants heterozygous for Rag1 and hemizygous for the two transgenes

Genotype
MGI:2665135

cx51

• Allelic Composition: Rag1^tm1Mom/Rag1⁺; Tg(LPV-TAg1135)11Tvd/0; Tg(TcrLCMV)327Sdz/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * DBA/2

mortality/aging

premature death ( J:47667 )

• survival time at which half of the mutants are sacrificed or die due to illness is 110 days

neoplasm

increased T cell derived lymphoma incidence ( J:47667 )

• 100% incidence of thymoma

• tumorigenesis is accelerated compared to mice hemizygous for Tg(LPV-TAg1135)11Tvd and heterozygous for Rag1

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:47667 )

• 100% incidence of thymoma

• tumorigenesis is accelerated compared to mice hemizygous for Tg(LPV-TAg1135)11Tvd and heterozygous for Rag1

hematopoietic system

increased T cell derived lymphoma incidence ( J:47667 )

• 100% incidence of thymoma

• tumorigenesis is accelerated compared to mice hemizygous for Tg(LPV-TAg1135)11Tvd and heterozygous for Rag1

immune system

increased T cell derived lymphoma incidence ( J:47667 )

• 100% incidence of thymoma

• tumorigenesis is accelerated compared to mice hemizygous for Tg(LPV-TAg1135)11Tvd and heterozygous for Rag1

Genotype
MGI:3687164

cx52

• Allelic Composition: H2^g7/H2^g7; Rag1^tm1Mom/Rag1^tm1Mom; Tg(TcraBDC12-4.1)10Jos/0; Tg(TcrbBDC12-4.1)82Gse/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD

endocrine/exocrine glands

insulitis ( J:111874 )

• 10-week-old diabetic mice show severe insulitis; disease is heterogeneous with some non-diabetic mice displaying it; infiltrate consists of CD4 cells, with an absence of CD8 T cells

immune system

insulitis ( J:111874 )

• 10-week-old diabetic mice show severe insulitis; disease is heterogeneous with some non-diabetic mice displaying it; infiltrate consists of CD4 cells, with an absence of CD8 T cells

increased susceptibility to autoimmune diabetes ( J:111874 )

• 15% of mice heterozygous for H2^g7 develop diabetes, compared to 50% of homozygous mice or 0% of non-H2^g7 mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:111874

Genotype
MGI:3687165

cx53

• Allelic Composition: H2^g7/H2^q; Rag1^tm1Mom/Rag1^tm1Mom; Tg(TcraBDC12-4.1)10Jos/0; Tg(TcrbBDC12-4.1)82Gse/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD

immune system

increased susceptibility to autoimmune diabetes ( J:111874 )

• 15% of mice heterozygous for the H2 alleles develop diabetes by 44 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:111874

Genotype
MGI:3687166

cx54

• Allelic Composition: H2^q/H2^q; Rag1^tm1Mom/Rag1^tm1Mom; Tg(TcraBDC12-4.1)10Jos/0; Tg(TcrbBDC12-4.1)82Gse/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD

immune system

decreased susceptibility to autoimmune diabetes ( J:111874 )

• O% of mice homozygous for H2^q develop diabetes

digestive/alimentary system

digestive/alimentary phenotype ( J:111874 )

N • mice do not develop insulitis

Genotype
MGI:3687163

cx55

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tg(TcraBDC12-4.1)10Jos/0; Tg(TcrbBDC12-4.1)82Gse/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD

homeostasis/metabolism

increased circulating glucose level ( J:111874 )

• mice are diabetic; diabetes assessed by blood glucose measures >250 mg/dl on two consectutive measurements

endocrine/exocrine glands

decreased pancreatic beta cell number ( J:111874 )

• diabetic mice have nearly complete destruction of insulin producing cells

decreased thymus weight ( J:111874 )

• thymus weight is variable, with some being normal and others having very low weight

• transgene expression in Rag1-deficient mice increases thymus cellularity and thymus weight almost to levels seen in NOD controls

immune system

decreased thymus weight ( J:111874 )

• thymus weight is variable, with some being normal and others having very low weight

• transgene expression in Rag1-deficient mice increases thymus cellularity and thymus weight almost to levels seen in NOD controls

increased double-positive T cell number ( J:111874 )

• mice have greater percentage of double-positive T cells (93%) in the thymus compared to other genotypes

decreased lymphocyte cell number ( J:111874 )

• mice are lymphopenic compared to Rag1-sufficient transgenic mice and control NOD animals; number of lymphocytes in peripheral blood is lower than in transgenic Rag1-sufficient mice both in percentage of total white blood cell count and absolute lymphocyte count

decreased CD4-positive, alpha-beta T cell number ( J:111874 )

• mice have lower percentage of single positive CD4+ T cells (3%) in the thymus compared to other genotypes

increased susceptibility to autoimmune diabetes ( J:111874 )

• mice develop spontaneous diabetes aged 4-32 weeks; diabetes develops only in mice with at least 1 copy of H-2^g7 (incidence is 50% with homozygosity, 15% in heterozygotes); both sexes of transgenic mice are equally affected

hematopoietic system

decreased thymus weight ( J:111874 )

• thymus weight is variable, with some being normal and others having very low weight

• transgene expression in Rag1-deficient mice increases thymus cellularity and thymus weight almost to levels seen in NOD controls

increased double-positive T cell number ( J:111874 )

• mice have greater percentage of double-positive T cells (93%) in the thymus compared to other genotypes

decreased lymphocyte cell number ( J:111874 )

• mice are lymphopenic compared to Rag1-sufficient transgenic mice and control NOD animals; number of lymphocytes in peripheral blood is lower than in transgenic Rag1-sufficient mice both in percentage of total white blood cell count and absolute lymphocyte count

decreased CD4-positive, alpha-beta T cell number ( J:111874 )

• mice have lower percentage of single positive CD4+ T cells (3%) in the thymus compared to other genotypes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:111874

Genotype
MGI:4940115

cx56

• Allelic Composition: Ctla4^tm1All/Ctla4^tm1All; Rag1^tm1Mom/Rag1^tm1Mom; Tg(TcrAND)53Hed/0
• Genetic Background: involves: 129S/Sv * 129X1/SvJ * C57BL/6 * SJL

immune system

abnormal T cell activation ( J:119845 )

• nearly all CD4+ T cells in aged mice exhibit an activated phenotype unlike in Tg(TcrAND)53Hed mice

• however, lymph node T cells maintain a naive phenotype in young mice

increased T cell proliferation ( J:119845 )

• CD4+ T cells exhibit increased primary and secondary antigen-specific proliferative responses compared to in Rag1^tm1Mom/Rag1^tm1Mom Tg(TcrAND)53Hed mice

increased interleukin-4 secretion ( J:119845 )

• in response to primary and secondary pigeon cytochrome c stimulation, the frequency of IL4-secreting T cells is increased compared to in Rag1^tm1Mom/Rag1^tm1Mom Tg(TcrAND)53Hed mice

hematopoietic system

abnormal T cell activation ( J:119845 )

• nearly all CD4+ T cells in aged mice exhibit an activated phenotype unlike in Tg(TcrAND)53Hed mice

• however, lymph node T cells maintain a naive phenotype in young mice

increased T cell proliferation ( J:119845 )

• CD4+ T cells exhibit increased primary and secondary antigen-specific proliferative responses compared to in Rag1^tm1Mom/Rag1^tm1Mom Tg(TcrAND)53Hed mice

cellular

increased T cell proliferation ( J:119845 )

• CD4+ T cells exhibit increased primary and secondary antigen-specific proliferative responses compared to in Rag1^tm1Mom/Rag1^tm1Mom Tg(TcrAND)53Hed mice

Genotype
MGI:3586594

cx57

• Allelic Composition: Igh-J^tm1Mcdl/Igh-J^tm1Mcdl; Igk-J^tm1Mcdl/Igk-J^tm1Mcdl; Rag1^tm1Mom/Rag1^tm1Mom; Tg(DO11.10)10Dlo/?
• Genetic Background: involves: 129S/Sv * BALB/c * C3H * C57BL/6

immune system

abnormal T cell differentiation ( J:100072 )

• the development of IL-4+IFNG- and IFNG+IL-4- T cells after immunization are increased but not if wild-type splenocytes are transferred into mutant mice

abnormal spleen germinal center morphology ( J:100072 )

• germinal center formation is increased in mutants but not if wild-type splenocytes are transferred into mutant mice

increased IgE level ( J:100072 )

• following immunization with a cross-linked OVA-HA antigen IgE levels are elevated by 2 orders of magnitude compared to mutant mice wild-type for Rag1; however serum Ig half-lives are normal

increased IgG level ( J:100072 )

• following immunization with a cross-linked OVA-HA antigen IgG titers are increased compared to mutant mice wild-type for Rag1, with IgG1 titers increased about 20-fold

hematopoietic system

abnormal T cell differentiation ( J:100072 )

• the development of IL-4+IFNG- and IFNG+IL-4- T cells after immunization are increased but not if wild-type splenocytes are transferred into mutant mice

abnormal spleen germinal center morphology ( J:100072 )

• germinal center formation is increased in mutants but not if wild-type splenocytes are transferred into mutant mice

increased IgE level ( J:100072 )

• following immunization with a cross-linked OVA-HA antigen IgE levels are elevated by 2 orders of magnitude compared to mutant mice wild-type for Rag1; however serum Ig half-lives are normal

increased IgG level ( J:100072 )

• following immunization with a cross-linked OVA-HA antigen IgG titers are increased compared to mutant mice wild-type for Rag1, with IgG1 titers increased about 20-fold

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hyper IgE recurrent infection syndrome 1		DOID:3261	OMIM:147060	J:100072

Genotype
MGI:3622066

cx58

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tnf^tm2Gkl/Tnf⁺
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6

immune system

small intestinal inflammation ( J:54056 )

• only minimal intestinal inflammation is seen, unlike in mice heterozygous for Tnf^tm2Gkl only

rheumatoid arthritis ( J:54056 )

• arthritis is similar to mice heterozygous for Tnf^tm2Gkl only

digestive/alimentary system

small intestinal inflammation ( J:54056 )

• only minimal intestinal inflammation is seen, unlike in mice heterozygous for Tnf^tm2Gkl only

skeleton

rheumatoid arthritis ( J:54056 )

• arthritis is similar to mice heterozygous for Tnf^tm2Gkl only

Genotype
MGI:3836413

cx59

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Vtcn1^tm1Lpc/Vtcn1^tm1Lpc
• Genetic Background: involves: 129S/SvEvBrd * 129S7/SvEvBrd * C57BL/6

mortality/aging

decreased susceptibility to bacterial infection induced morbidity/mortality ( J:145712 )

• Listeria-infected mice die by day 15 post-infection compared to Rag1^tm1Mom homozygotes that die at day 4 post-infection

immune system

abnormal neutrophil differentiation ( J:145712 )

• proliferation of Gr1+CD11b+ neutrophil progenitors is increased compared to in Rag1^tm1Mom homozygotes

increased spleen weight ( J:145712 )

increased neutrophil cell number ( J:145712 )

• compared to in Rag1^tm1Mom homozygotes

decreased susceptibility to bacterial infection ( J:145712 )

• mice infected with Listeria exhibit increased neutrophil numbers and increased bacterial clearance compared to similarly treated Rag1^tm1Mom homozygotes

• however, depletion of Gr-1+ neutrophils increases bacterial load in Listeria-infected mice

decreased susceptibility to bacterial infection induced morbidity/mortality ( J:145712 )

• Listeria-infected mice die by day 15 post-infection compared to Rag1^tm1Mom homozygotes that die at day 4 post-infection

hematopoietic system

abnormal neutrophil differentiation ( J:145712 )

• proliferation of Gr1+CD11b+ neutrophil progenitors is increased compared to in Rag1^tm1Mom homozygotes

increased spleen weight ( J:145712 )

increased neutrophil cell number ( J:145712 )

• compared to in Rag1^tm1Mom homozygotes

cellular

abnormal neutrophil differentiation ( J:145712 )

• proliferation of Gr1+CD11b+ neutrophil progenitors is increased compared to in Rag1^tm1Mom homozygotes

growth/size/body

increased spleen weight ( J:145712 )

Genotype
MGI:3719168

cx60

• Allelic Composition: Bcl6b^tm2Dent/Bcl6b^tm2Dent; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: involves: 129/Sv * 129S7/SvEvBrd * C57BL/6

hematopoietic system

abnormal blood cell morphology/development ( J:123621 )

• mice have decreased hematopoeitic progenitor cell (HPC) number and cycling in the spleen compared to in Bcl6b^tm2Dent homozygotes but levels are similar to those in wild-type mice

• mice have decreased HPC number and cycling in the bone marrow similar to in Bcl6b^tm2Dent homozygotes

decreased lymphocyte cell number ( J:123621 )

• mice lack mature lymphocytes

immune system

decreased lymphocyte cell number ( J:123621 )

• mice lack mature lymphocytes

Genotype
MGI:2665126

cx61

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tg(LPV-TAg1135)11Tvd/0
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA/2

mortality/aging

premature death ( J:47667 )

• survival time at which half of the mutants are sacrificed or die due to illness is 238 days

neoplasm

increased T cell derived lymphoma incidence ( J:47667 )

• 85% incidence of thymoma

• tumors arise more slowly or with longer latency than in single hemizygous Tg(LPV-TAg1135)11Tvd mice, with mutants living 44% longer than controls

hematopoietic system

increased T cell derived lymphoma incidence ( J:47667 )

• 85% incidence of thymoma

• tumors arise more slowly or with longer latency than in single hemizygous Tg(LPV-TAg1135)11Tvd mice, with mutants living 44% longer than controls

abnormal T cell receptor V(D)J recombination ( J:47667 )

• inactive V(D)J recombination

immune system

increased T cell derived lymphoma incidence ( J:47667 )

• 85% incidence of thymoma

• tumors arise more slowly or with longer latency than in single hemizygous Tg(LPV-TAg1135)11Tvd mice, with mutants living 44% longer than controls

abnormal T cell receptor V(D)J recombination ( J:47667 )

• inactive V(D)J recombination

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:47667 )

• 85% incidence of thymoma

• tumors arise more slowly or with longer latency than in single hemizygous Tg(LPV-TAg1135)11Tvd mice, with mutants living 44% longer than controls

Genotype
MGI:2665123

cx62

• Allelic Composition: Rag1^tm1Mom/Rag1⁺; Tg(LPV-TAg1135)11Tvd/0
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA/2

mortality/aging

premature death ( J:47667 )

• survival time at which half of the mutants are sacrificed or die due to illness is 165 days

neoplasm

increased T cell derived lymphoma incidence ( J:47667 )

• 100% incidence of thymoma

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:47667 )

• 100% incidence of thymoma

immune system

increased T cell derived lymphoma incidence ( J:47667 )

• 100% incidence of thymoma

hematopoietic system

increased T cell derived lymphoma incidence ( J:47667 )

• 100% incidence of thymoma

Genotype
MGI:3687126

cx63

• Allelic Composition: H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru; Rag1^tm1Mom/Rag1^tm1Mom; Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
• Genetic Background: NOD.Cg-Rag1^tm1Mom H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

cardiovascular system

cardiovascular system phenotype ( J:113267 )

N • animals have normal sized hearts, normal ECG, and show no sign of autoimmune pathology

enlarged heart ( J:113267 )

• recipient animals develop cardiomegaly by 12 weeks after transfer

prolonged PR interval ( J:113267 )

• mice receiving splenic lymphocytes from animals with heart block display first-degree heart block as early as 2 weeks after transfer, with 50% progressing to complete heart block in 8 weeks

heart inflammation ( J:113267 )

• recipient animals develop mononuclear cell infiltrates within heart wall by 12 weeks after transplant

myocarditis ( J:113267 )

• when young mice receive splenic lymphocytes from older NOD.DQ8/H2Ab-1 mice with heart block, myocarditis is triggered in 100% of recipients

immune system

heart inflammation ( J:113267 )

• recipient animals develop mononuclear cell infiltrates within heart wall by 12 weeks after transplant

myocarditis ( J:113267 )

• when young mice receive splenic lymphocytes from older NOD.DQ8/H2Ab-1 mice with heart block, myocarditis is triggered in 100% of recipients

increased autoantibody level ( J:113267 )

• anticardiac myosin autoantibodies reach a titer of 1:10000 in recipient mice at 12 weeks posttransfer

abnormal response to transplant ( J:113267 )

• younger mice receiving splenic lymphocytes from older DQ8 transgenic, H2-Ab1-null mice with heart block develop heart block, myocarditis, and autoantibodies

• when younger mice receive serum from the same older animals, no cardiac pathology is observed

• recipient mice receiving CD4 T cells from older donor animals with heart block develop heart block as early as 4 weeks posttransfer; all animals are diseased by 12 weeks and upon necropsy, heart are enlarged

• mononuclear cells are more numerous and infiltrates more widespread than in animals that receive total splenocytes (containing CD4 T cells) in the myocardium

• disease onset is somewhat accelerated compared to recipients receiving total lymphocytes;

growth/size/body

enlarged heart ( J:113267 )

• recipient animals develop cardiomegaly by 12 weeks after transfer

Genotype
MGI:3687028

cx64

• Allelic Composition: H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru; Rag1^tm1Mom/Rag1^tm1Mom; Tg(HLA-DQA1,HLA-DQB1)73Myl/0
• Genetic Background: NOD.Cg-Rag1^tm1Mom H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)73Myl

cardiovascular system

myocarditis ( J:88055 )

• mice do not develop spontaneous myocarditis like NOD.B6-H2Ab1^tm1Gru-Tg(HLA-DQA1,HLA-DQB1)73 mice

immune system

myocarditis ( J:88055 )

• mice do not develop spontaneous myocarditis like NOD.B6-H2Ab1^tm1Gru-Tg(HLA-DQA1,HLA-DQB1)73 mice

abnormal response to transplant ( J:88055 )

• injection of splenocytes from myocarditis-affected donors into healthy transgenic mice results in acute onset of symptoms of severe heart failure 3 weeks post-transfer, reproducing symptoms of the donor mice

• injection of serum from diseased donors with high autoantibody titer does not result in myocarditis

Genotype
MGI:3813939

cx65

• Allelic Composition: Il2rg^tm1Wjl/Y; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ

growth/size/body

thymus cyst ( J:140388 )

♂ • thymus contains large cysts

immune system

abnormal thymus morphology ( J:140388 )

♂ • no lymphoid cells are present

absent thymus cortex ( J:140388 )

♂ • no defined cortical region is observed

absent thymus medulla ( J:140388 )

♂ • no defined medullary region is observed

thymus cyst ( J:140388 )

♂ • thymus contains large cysts

absent NK T cells ( J:140388 )

♂ • natural killer cell (NK; DX5+LGL+ cells) are absent

decreased macrophage cell number ( J:140388 )

♂ • levels are Gr-1-ve Mac-1+ve macrophages are reduced

abnormal spleen morphology ( J:140388 )

♂ • spleen contains mainly myeloid-like cells and few lymphoid cells

decreased spleen B cell follicle number ( J:140388 )

♂ • spleen contains no follicles (or germinal centers)

abnormal adaptive immunity ( J:140388 )

♂ • mature T and B cell populations are absent

♂ • there are diminished CD3+CD4+ and CD3+CD8+ T cells and Igk+ light chain+ B cells in the spleen

abnormal innate immunity ( J:140388 )

♂ • cells functioning in innate immunity are severely decreased in number

abnormal response to transplant ( J:140388 )

♂ • irradiated mice engrafted with human hematopoietic stem cells (HSCs) show much greater engraftment of human hematopoietic cells at 12 weeks than control NOD.129S7(B6)-Rag1^tm1Mom homozygotes

♂ • percentages of human CD45+ cells engrafted in bone marrow are higher than in NOD.129S7(B6)-Rag1^tm1Mom homozygotes

♂ • levels of human CD45+ cell and CD3+ T cell engraftment are higher in spleens than in NOD.129S7(B6)-Rag1^tm1Mom mice

♂ • CD4:CD8 human T cell ratios that are close to normal physiological values and high levels of human B cells are observed in spleens of mice compared to NOD.129S7(B6)-Rag1^tm1Mom mice

♂ • engraftment of human lymphohematopoietic cells in blood and thymus, and peripheral blood mononuclear cells (PMBC) engraftment are higher than in NOD.129S7(B6)-Rag1^tm1Mom mice

hematopoietic system

abnormal thymus morphology ( J:140388 )

♂ • no lymphoid cells are present

absent thymus cortex ( J:140388 )

♂ • no defined cortical region is observed

absent thymus medulla ( J:140388 )

♂ • no defined medullary region is observed

thymus cyst ( J:140388 )

♂ • thymus contains large cysts

absent NK T cells ( J:140388 )

♂ • natural killer cell (NK; DX5+LGL+ cells) are absent

decreased macrophage cell number ( J:140388 )

♂ • levels are Gr-1-ve Mac-1+ve macrophages are reduced

abnormal spleen morphology ( J:140388 )

♂ • spleen contains mainly myeloid-like cells and few lymphoid cells

decreased spleen B cell follicle number ( J:140388 )

♂ • spleen contains no follicles (or germinal centers)

endocrine/exocrine glands

abnormal thymus morphology ( J:140388 )

♂ • no lymphoid cells are present

absent thymus cortex ( J:140388 )

♂ • no defined cortical region is observed

absent thymus medulla ( J:140388 )

♂ • no defined medullary region is observed

thymus cyst ( J:140388 )

♂ • thymus contains large cysts

Genotype
MGI:3817776

cx66

• Allelic Composition: Ins2^Akita/Ins2^Akita; Prf1^tm1Sdz/Prf1^tm1Sdz; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: NOD.Cg-Rag1^tm1Mom Ins2^Akita Prf1^tm1Sdz

mortality/aging

postnatal lethality, complete penetrance ( J:138005 )

• mice die prior to weaning

Genotype
MGI:3817777

cx67

• Allelic Composition: Ins2^Akita/Ins2⁺; Prf1^tm1Sdz/Prf1^tm1Sdz; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: NOD.Cg-Rag1^tm1Mom Ins2^Akita Prf1^tm1Sdz

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:138005 )

• islets exhibit progressively altered morphology

• insulin level is lower compared to Ins2-wild-type mice at 50 days of age and continues to diminish with age

hematopoietic system

increased erythrocyte cell number ( J:138005 )

• erythrocyte/erythocyte lineages (Ter 119+) are increased as compared to NOD controls

increased granulocyte number ( J:138005 )

• percentage of granulocytes is elevated compared to NOD/Lt

absent mature B cells ( J:138005 )

• lacking in mutant animals

absent T cells ( J:138005 )

• mature T cells are absent in mutant animals

increased macrophage cell number ( J:138005 )

• percentage of granulocytes is elevated

increased monocyte cell number ( J:138005 )

• percentage of granulocytes is elevated

immune system

increased granulocyte number ( J:138005 )

• percentage of granulocytes is elevated compared to NOD/Lt

absent mature B cells ( J:138005 )

• lacking in mutant animals

absent T cells ( J:138005 )

• mature T cells are absent in mutant animals

increased macrophage cell number ( J:138005 )

• percentage of granulocytes is elevated

increased monocyte cell number ( J:138005 )

• percentage of granulocytes is elevated

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:138005 )

N • spontaneously hyperglycemic mice are restored to euglycemia after receiving islet transplants at a dose of 4000 islet equivalents (IEQ) and remain euglycemic for the length of observation; at levels of 2000 and 3000 IEQ, mice display a drop in blood sugar, but eventually return to hyperglycemic status

abnormal glucose homeostasis ( J:138005 )

• glucose regulation is impaired as early as 3 weeks of age in nearly all mice

hyperglycemia ( J:138005 )

• male mice show greater susceptibility to develop hyperglycemia than females

Genotype
MGI:3580416

cx68

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Prf1^tm1Sdz/Prf1^tm1Sdz
• Genetic Background: NOD.Cg-Rag1^tm1Mom Prf1^tm1Sdz/Sz

mortality/aging

premature death ( J:109843 )

• mean lifespan is 262+/-21 days

immune system

abnormal thymus cortex morphology ( J:109843 )

• thymus lacks a clearly defined cortex

thymus hypoplasia ( J:109843 )

• lymphoid cells are severely reduced in thymuses

increased T cell derived lymphoma incidence ( J:109843 )

increased immature B cell number ( J:109843 )

• IgLkappa- B220+ immature B cells are increased six-fold as compared to NOD controls

increased granulocyte number ( J:109843 )

• numbers of granulocytes are increased in comparison to NOD controls, however, in comparison to NOD-Rag^null numbers are decreased

decreased mature B cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells

increased NK cell number ( J:109843 )

• numbers of NK cells are increased in comparison to NOD controls

decreased CD4-positive, alpha-beta T cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells

decreased CD8-positive, alpha-beta T cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells

increased macrophage cell number ( J:109843 )

• numbers of macrophages are increased in comparison to NOD controls

spleen hypoplasia ( J:109843 )

• nucleated spleen cells are reduced 14 fold in 8-11 week old mice as compared to NOD control

abnormal spleen white pulp morphology ( J:109843 )

• spleen lacks lymphoid follicles

decreased immunoglobulin level ( J:109843 )

• no serum immunoglobulin is detected in 176-362 day old mice

impaired natural killer cell mediated cytotoxicity ( J:109843 )

• poly I:C stimulated spleen cells exhibit extremely low levels of NK cell cyotoxic activity

abnormal lymph node cortex morphology ( J:109843 )

• lymph nodes lack follicles

abnormal level of surface class II molecules ( J:109843 )

• four to five-fold decrease in cells expressing I-A^g7 as compared to NOD control

abnormal response to transplant ( J:109843 )

• following IP injection of human PMBC, peripheral blood has a fivefold increase in the percentage of human lymphoid cells as compared to NOD-Rag^null controls

• peripheral blood has a 13-fold increase in engraftment of human CD4+ T cells

• spleens have a 9-fold increase in engraftment of human CD45+ cells and a 20-fold increase in human CD4+ cells as compared to control, although there is no significant difference in engraftment of human CD8+ cells

• 6-8 weeks after IP injection, bone marrow exhibits a 12-fold increase in engraftment of human cord blood cells

neoplasm

increased T cell derived lymphoma incidence ( J:109843 )

hematopoietic system

abnormal thymus cortex morphology ( J:109843 )

• thymus lacks a clearly defined cortex

thymus hypoplasia ( J:109843 )

• lymphoid cells are severely reduced in thymuses

increased T cell derived lymphoma incidence ( J:109843 )

increased immature B cell number ( J:109843 )

• IgLkappa- B220+ immature B cells are increased six-fold as compared to NOD controls

increased granulocyte number ( J:109843 )

• numbers of granulocytes are increased in comparison to NOD controls, however, in comparison to NOD-Rag^null numbers are decreased

decreased mature B cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells

increased NK cell number ( J:109843 )

• numbers of NK cells are increased in comparison to NOD controls

decreased CD4-positive, alpha-beta T cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells

decreased CD8-positive, alpha-beta T cell number ( J:109843 )

• spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells

increased macrophage cell number ( J:109843 )

• numbers of macrophages are increased in comparison to NOD controls

spleen hypoplasia ( J:109843 )

• nucleated spleen cells are reduced 14 fold in 8-11 week old mice as compared to NOD control

abnormal spleen white pulp morphology ( J:109843 )

• spleen lacks lymphoid follicles

decreased immunoglobulin level ( J:109843 )

• no serum immunoglobulin is detected in 176-362 day old mice

impaired natural killer cell mediated cytotoxicity ( J:109843 )

• poly I:C stimulated spleen cells exhibit extremely low levels of NK cell cyotoxic activity

endocrine/exocrine glands

abnormal thymus cortex morphology ( J:109843 )

• thymus lacks a clearly defined cortex

thymus hypoplasia ( J:109843 )

• lymphoid cells are severely reduced in thymuses

increased T cell derived lymphoma incidence ( J:109843 )

Genotype
MGI:3844697

cx69

• Allelic Composition: Prf1^tm1Sdz/Prf1^tm1Sdz; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: NOD.Cg-Rag1^tm1Mom Prf1^tm1Sdz/SzJ

homeostasis/metabolism

increased circulating glucose level ( J:91764 )

• streptozotocin-treated mice exhibit increased serum glucose levels that can be restored transiently to euglycemia by transplanting islet cells from Prkdc^scid/Prkdc^scid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice

• 70% of streptozotocin-treated mice transplanted with islet cells from Prkdc^scid/Prkdc^scid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice and HLA-A2 negative human peripheral blood mononuclear cells exhibit increased glucose serum levels

• however, all of streptozotocin-treated mice transplanted with islet cells from Prkdc^scid/Prkdc^scid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice and HLA-A2 positive human peripheral blood mononuclear cells exhibit euglycemia

immune system

abnormal response to transplant ( J:91764 )

• streptozotocin-treated mice transplanted with islet cells from Prkdc^scid/Prkdc^scid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice and HLA-A2 negative human peripheral blood mononuclear cells exhibit destruction of engrafted islet cells

Genotype
MGI:3618788

cx70

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tg(TcraAI4)1Dvs/0; Tg(TcrbAI4)1Dvs/0
• Genetic Background: NOD.Cg-Rag1^tm1Mom Tg(TcraAI4)1Dvs Tg(TcrbAI4)1Dvs/Dvs

immune system

increased susceptibility to autoimmune diabetes ( J:94192 )

• females have a greatly increased rate of diabetes development compared to non-transgenic NOD controls (100% incidence by 6 weeks of age)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:94192

Genotype
MGI:3574972

cx71

• Allelic Composition: Foxp3^tm1.1Ayr/Y; Rag1^tm1Mom/Rag1^tm1Mom; Tg(TcraTcrb)425Cbn/0
• Genetic Background: Not Specified

immune system

immune system phenotype ( J:97029 )

♂N • mice exhibit no differences in thymocyte and peripheral T cell subpopulations and normal antigen sensitivity, costimulation requirement and proliferative capacity of nonregulatory CD4+ T cells

normal phenotype

no abnormal phenotype detected ( J:97029 )

♂ • mice were healthy and phenotypically indistinguishable from controls