Phenotypes associated with this allele

• Allele Symbol: Rb1^tm2Brn
• Allele Name: targeted mutation 2, Anton Berns
• Allele ID: MGI:1931018
• Summary: 52 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Rb1^tm2Brn/Rb1^tm2Brn	involves: 129	MGI:4437463
cn2	Rb1^tm2Brn/Rb1^tm2Brn	involves: 129 * BALB/c	MGI:4353993
cn3	Gt(ROSA)26Sor^tm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor^+ Rb1^tm2Brn/Rb1^tm2Brn Tg(Gfap-cre)2Brn/0	either: (involves: 129 * 129P2/OlaHsd * FVB/N) or (involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB/N)	MGI:5437516
cn4	Gt(ROSA)26Sor^tm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor^+ Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Gfap-cre)2Brn/0	either: (involves: 129 * 129P2/OlaHsd * FVB/N) or (involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB/N)	MGI:5437517
cn5	Rb1^tm2Brn/Rb1^tm2Brn Tg(MMTV-cre)105Ayn/0	FVB.Cg-Rb1^tm2Brn Tg(MMTV-cre)105Ayn	MGI:4837143
cn6	Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(MMTV-cre)105Ayn/0	FVB.Cg-Trp53^tm1Brn Rb1^tm2Brn Tg(MMTV-cre)105Ayn	MGI:4837145
cn7	Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Lejo/Trp53^tm1Lejo	involves: 129	MGI:5441551
cn8	Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Ren-cre)#Kwg/0	involves: 129 * 129P2/OlaHsd	MGI:5662454
cn9	Prkar1a^tm1.2Lsk/Prkar1a^+ Rb1^tm2Brn/Rb1^+ Tg(Col1a1-cre)1Kry/0 Trp53^tm1Brn/Trp53^tm1Brn	involves: 129 * 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB/N	MGI:5796166
cn10	Prkar1a^tm1.2Lsk/Prkar1a^+ Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Col1a1-cre)1Kry/0	involves: 129 * 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB/N	MGI:5796167
cn11	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
cn12	Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^tm1Sor Pten^tm1Mro/Pten^tm1Mro Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn	involves: 129 * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * FVB/N	MGI:5563247
cn13	Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^tm1Sor Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn	involves: 129 * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * FVB/N	MGI:5563244
cn14	Dlg2^tm1a(EUCOMM)Wtsi/Dlg2^tm1a(EUCOMM)Wtsi Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Col1a1-cre)1Kry/0	involves: 129 * 129P2/OlaHsd * C57BL/6N * FVB/N	MGI:7484008
cn15	Calca^tm1.1(cre/ERT2)Ptch/Calca^+ Trp53^tm1Brn/Trp53^tm1Brn Rb1^tm2Brn/Rb1^tm2Brn	involves: 129 * 129P2/OlaHsd * FVB/N	MGI:5460840
cn16	Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Gfap-cre)2Brn/0	involves: 129 * 129P2/OlaHsd * FVB/N	MGI:5437518
cn17	Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Col1a1-cre)1Kry/0	involves: 129 * 129P2/OlaHsd * FVB/N	MGI:5796161
cn18	Rb1^tm2Brn/Rb1^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Col1a1-cre)1Kry/0	involves: 129 * 129P2/OlaHsd * FVB/N	MGI:5796164
cn19	Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(BGLAP-cre)1Clem/0	involves: 129 * 129P2/OlaHsd * FVB/NJ	MGI:7482566
cn20	Gt(ROSA)26Sor^tm1(CAG-MYCN,-luc)Jhsc/Gt(ROSA)26Sor^+ Pten^tm2.1Ppp/Pten^tm2.1Ppp Rb1^tm2Brn/Rb1^tm2Brn Tg(Pbsn-cre)4Prb/0	involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:7277819
cn21	Gt(ROSA)26Sor^tm1(CAG-MYCN,-luc)Jhsc/Gt(ROSA)26Sor^+ Pten^tm2.1Ppp/Pten^tm2.1Ppp Rb1^tm2Brn/Rb1^+ Tg(Pbsn-cre)4Prb/0	involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:7277820
cn22	Pten^tm2.1Ppp/Pten^tm2.1Ppp Rb1^tm2Brn/Rb1^tm2Brn Tg(Pbsn-cre)4Prb/0	involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:7277828
cn23	Rb1^tm2Brn/Rb1^tm2Brn Rbl1^tm1Tyj/Rbl1^tm1Tyj Rbl2^tm2Tyj/Rbl2^tm2Tyj	involves: 129 * 129S2/SvPas * 129S4/SvJae	MGI:5789748
cn24	Rb1^tm2Brn/Rb1^tm2Brn Rbl2^tm1Tyj/Rbl2^tm1Tyj Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds	involves: 129 * 129S2/SvPas * FVB/N	MGI:3710679
cn25	Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^tm1Sor Pten^tm1Mro/Pten^tm1Mro Rb1^tm2Brn/Rb1^tm2Brn	involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB	MGI:5563246
cn26	Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brd/Trp53^+ Tg(Rbp3-cre)1Brn/0	involves: 129 * 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:2653661
cn27	Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brd/Trp53^tm1Brd Tg(Gfap-cre)2Brn/0	involves: 129 * 129S7/SvEvBrd * FVB/N	MGI:3804216
cn28	Rb1^tm2Brn/Rb1^tm2Brn Tg(Pou4f3-cre)1Devet/0	involves: 129 * 129S/SvEv	MGI:3639920
cn29	Ccnd3^tm1Pisc/Ccnd3^tm1Pisc Rb1^tm2Brn/Rb1^tm2Brn Tg(Mx1-cre)1Cgn/0	involves: 129 * C57BL/6 * CBA	MGI:5468652
cn30	Rb1^tm2Brn/Rb1^tm2Brn Tg(Cyp1a1-cre)1Dwi/0	involves: 129 * C57BL/6 * CBA	MGI:5614112
cn31	Rb1^tm2Brn/Rb1^tm2Brn Tg(KRT14-cre)8Brn/0 Tg(KRT5-Akt1*)Jmpa/0	involves: 129 * C57BL/6 * DBA/2 * DBA/2J * FVB/N	MGI:3842836
cn32	Rb1^tm2Brn/Rb1^tm2Brn Tg(Col1a1-cre)1Bek/0	involves: 129 * CD-1	MGI:3574808
cn33	Rb1^tm2Brn/Rb1^tm2Brn Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds	involves: 129 * FVB	MGI:3710677
cn34	Rb1^tm2Brn/Rb1^tm2Brn Tg(Gfap-cre)2Brn/0	involves: 129 * FVB/N	MGI:3804218
cn35	Rb1^tm2Brn/Rb1^tm2Brn Tg(Rbp3-cre)1Brn/0	involves: 129 * FVB/N	MGI:2653660
cn36	Nell1^tm1Kuv/Nell1^tm1Kuv Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(BGLAP-cre)1Clem/0	involves: 129 * FVB/NJ	MGI:7482567
cn37	Rb1^tm2Brn/Rb1^+ Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd	MGI:5704166
cn38	Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd	MGI:4437461
cn39	Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^+	involves: 129P2/OlaHsd	MGI:4437462
cn40	Rb1^tm1Tyj/Rb1^tm2Brn Rbl1^tm1Tyj/Rbl1^tm1Tyj Trp53^tm1Brn/Trp53^tm1Tyj Tg(Chx10-EGFP/cre,-ALPP)2Clc/0	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL	MGI:3710239
cn41	Rb1^tm1Tyj/Rb1^tm2Brn Rbl1^tm1Tyj/Rbl1^tm1Tyj Trp53^tm1Brn/Trp53^tm1Brn Tg(Chx10-EGFP/cre,-ALPP)2Clc/0	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL	MGI:3710238
cn42	Rb1^tm1Tyj/Rb1^tm2Brn Rbl1^tm1Tyj/Rbl1^+ Tg(Chx10-EGFP/cre,-ALPP)2Clc/0	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL	MGI:3710241
cn43	Rb1^tm1Tyj/Rb1^tm2Brn Rbl1^tm1Tyj/Rbl1^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Chx10-EGFP/cre,-ALPP)2Clc/0	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL	MGI:3710240
cn44	Rb1^tm2Brn/Rb1^tm2Brn Rbl1^tm1Htr/Rbl1^tm1Htr Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd * CD-1	MGI:3707498
cn45	Rb1^tm2Brn/Rb1^tm2Brn Rbl1^tm1Htr/Rbl1^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd * CD-1	MGI:3707502
cn46	Rb1^tm2Brn/Rb1^tm2Brn Rbl1^tm1Htr/Rbl1^+ Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd * CD-1	MGI:3707499
cn47	Rb1^tm2Brn/Rb1^tm2Brn Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd * CD-1	MGI:3707497
cn48	Rb1^tm2Brn/Rb1^tm2Brn Rbl1^tm1Htr/Rbl1^tm1Htr Tg(Pcp2-cre)756Mro/0	involves: 129P2/OlaHsd * FVB	MGI:3707500
cn49	Rb1^tm2Brn/Rb1^tm2Brn Tg(Pcp2-cre)756Mro/0	involves: 129P2/OlaHsd * FVB	MGI:3707501
cn50	Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Gfap-cre)2Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3804217
cn51	Ccnd3^tm1Pisc/Ccnd3^tm1Pisc Cdkn1b^tm1Mlf/Cdkn1b^tm1Mlf Rb1^tm2Brn/Rb1^tm2Brn Tg(Mx1-cre)1Cgn/0	involves: 129S4/SvJaeSor * C57BL/6 * CBA	MGI:5468653
cn52	Rb1^tm1Dwg/Rb1^tm2Brn Tg(Chx10-EGFP/cre,-ALPP)2Clc/0	involves: 129/Sv * C57BL/6 * SJL	MGI:3618365

Genotype
MGI:4437463

cn1

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn
• Genetic Background: involves: 129

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

neoplasm

neoplasm ( J:86077 , J:157319 )

N • mice treated with a cre-expressing adenovirus exhibit normal lungs with no lesions (J:86077)

N • following treatment with cre-expressing adenovirus, mice do not develop lung tumors (J:157319)

respiratory system

respiratory system phenotype ( J:86077 )

N • mice treated with a cre-expressing adenovirus exhibit normal lungs with no lesions

Genotype
MGI:4353993

cn2

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn
• Genetic Background: involves: 129 * BALB/c

adipose tissue

abnormal white adipose tissue morphology ( J:129672 )

• following transfection with adeno-cre, preadipocyte differentiation is almost completely blocked unlike in wild-type cells

Genotype
MGI:5437516

cn3

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-Bmi1,-EGFP)Nki}/Gt(ROSA)26Sor⁺; Rb1^tm2Brn/Rb1^tm2Brn; Tg(Gfap-cre)2Brn/0
• Genetic Background: either: (involves: 129 * 129P2/OlaHsd * FVB/N) or (involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB/N)

mortality/aging

premature death ( J:187257 )

neoplasm

neoplasm ( J:187257 )

N • mice do not develop medulloblastoma

increased pituitary gland tumor incidence ( J:187257 )

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:187257 )

nervous system

increased pituitary gland tumor incidence ( J:187257 )

Genotype
MGI:5437517

cn4

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-Bmi1,-EGFP)Nki}/Gt(ROSA)26Sor⁺; Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Gfap-cre)2Brn/0
• Genetic Background: either: (involves: 129 * 129P2/OlaHsd * FVB/N) or (involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB/N)

neoplasm

increased pituitary gland tumor incidence ( J:187257 )

increased medulloblastoma incidence ( J:187257 )

• as in Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Gfap-cre)2Brn mice

increased carcinoma incidence ( J:187257 )

• large cell carcinoma

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:187257 )

nervous system

increased pituitary gland tumor incidence ( J:187257 )

increased medulloblastoma incidence ( J:187257 )

• as in Rb1^tm2Brn/Rb1^tm2Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Gfap-cre)2Brn mice

Genotype
MGI:4837143

cn5

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(MMTV-cre)105Ayn/0
• Genetic Background: FVB.Cg-Rb1^tm2Brn Tg(MMTV-cre)105Ayn

neoplasm

neoplasm ( J:165292 )

N • mice do not develop mammary neoplasms

Genotype
MGI:4837145

cn6

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(MMTV-cre)105Ayn/0
• Genetic Background: FVB.Cg-Trp53^tm1Brn Rb1^tm2Brn Tg(MMTV-cre)105Ayn

neoplasm

increased mammary gland tumor incidence ( J:165292 )

• 15 of 17 mice develop mammary neoplasms

• mammary tumor cells exhibit increased genomic instability compared to in Trp53^tm1Brn/Trp53^tm1Brn Tg(MMTV-cre)105Ayn mice

increased tumor growth/size ( J:165292 )

• cell proliferation in mammary carcinomas is increased compared to in Trp53^tm1Brn/Trp53^tm1Brn Tg(MMTV-cre)105Ayn mice

increased carcinoma incidence ( J:165292 )

• 10 of 43 neoplasms are well-differentiated carcinomas

• while one tumor is an adenosquamous carcinoma the remaining tumors are poorly differentiated carcinomas with spindle or polygonal, frequently pleomorphic cells

increased squamous cell carcinoma incidence ( J:165292 )

• 1 adenosquamous carcinoma

increased lung tumor incidence ( J:165292 )

• 4 of 40 mice develop lung metastasis

cellular

chromosomal instability ( J:165292 )

• mammary tumor cells exhibit increased genomic instability compared to in Trp53^tm1Brn/Trp53^tm1Brn Tg(MMTV-cre)105Ayn mice

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:165292 )

• 15 of 17 mice develop mammary neoplasms

• mammary tumor cells exhibit increased genomic instability compared to in Trp53^tm1Brn/Trp53^tm1Brn Tg(MMTV-cre)105Ayn mice

integument

increased mammary gland tumor incidence ( J:165292 )

• 15 of 17 mice develop mammary neoplasms

• mammary tumor cells exhibit increased genomic instability compared to in Trp53^tm1Brn/Trp53^tm1Brn Tg(MMTV-cre)105Ayn mice

respiratory system

increased lung tumor incidence ( J:165292 )

• 4 of 40 mice develop lung metastasis

Genotype
MGI:5441551

cn7

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Lejo/Trp53^tm1Lejo
• Genetic Background: involves: 129

mortality/aging

premature death ( J:187012 )

• adenovirus-FLPe/IRES/Cre (Ad-FIC) induces a dose dependent increase in mortality with no mice surviving to 55 weeks post infection at concentrations greater than or equal to 5.00E+06 infectious units (iu)

• no mice survive to 40 weeks post infection when dosed with 5.00E+07 iu of Ad-FIC

neoplasm

increased lung small cell carcinoma incidence ( J:187012 )

• following infection with Ad-FIC

• early stage tumors are detected by 16 weeks post infection with Ad-FIC and late stage tumors are detected by about 32 weeks post infection

respiratory system

abnormal lung morphology ( J:187012 )

• neuroendocrine hyperplasia is detected at 8 weeks post infection with Ad-FIC

increased lung small cell carcinoma incidence ( J:187012 )

• following infection with Ad-FIC

• early stage tumors are detected by 16 weeks post infection with Ad-FIC and late stage tumors are detected by about 32 weeks post infection

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lung small cell carcinoma		DOID:5409	OMIM:182280	J:187012

Genotype
MGI:5662454

cn8

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Ren-cre)#Kwg/0
• Genetic Background: involves: 129 * 129P2/OlaHsd

neoplasm

increased glucagonoma incidence ( J:216559 )

• pancreatic tumors and liver metastasis express high levels of glucagon and mice exhibit increased circulating glucagon levels indicating that tumors are glucagonoma

increased pancreatic islet cell carcinoma incidence ( J:216559 )

• mice develop pancreatic neuroendocrine tumors that are classified as metastatic islet cell carcinoma; tumors are nodular and highly vascularized

• marker analysis indicates that both the primary pancreatic tumor and the liver metastases are pancreatic neuroendocrine in origin

increased metastatic potential ( J:216559 )

• metastasis to the liver and lymph node is seen; liver metastases are nodular and highly vascularized

• liver also contains many separate metastatic foci

increased sarcoma incidence ( J:216559 )

• mice develop subcutaneous tumors infrequently at around 3-4 months of age; these tumors have a solid growth pattern and are consistent with high-grade vascular sarcoma

endocrine/exocrine glands

increased glucagonoma incidence ( J:216559 )

• pancreatic tumors and liver metastasis express high levels of glucagon and mice exhibit increased circulating glucagon levels indicating that tumors are glucagonoma

increased pancreatic islet cell carcinoma incidence ( J:216559 )

• mice develop pancreatic neuroendocrine tumors that are classified as metastatic islet cell carcinoma; tumors are nodular and highly vascularized

• marker analysis indicates that both the primary pancreatic tumor and the liver metastases are pancreatic neuroendocrine in origin

mortality/aging

decreased tumor-free survival time ( J:216559 )

• primary mortality is from metastatic pancreatic neuroendocrine disease with lethal onset beginning at around 22 weeks of age

• in rare instances, mice develop subcutaneous tumors and need to be euthanized at around 12-16 weeks of age and in even more rare cases, mice die as early as 8 weeks of age of unknown causes; these cases constitute about 12% of mice

homeostasis/metabolism

increased circulating glucagon level ( J:216559 )

• mice show increased circulating glucagon levels at 4, 5 and 6 months but not at 2 months of age

growth/size/body

decreased body weight ( J:216559 )

• 32% reduction in body weight of sick mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
adenoma		DOID:657		J:216559
pancreatic carcinoma		DOID:4905	OMIM:260350	J:216559

Genotype
MGI:5796166

cn9

• Allelic Composition: Prkar1a^tm1.2Lsk/Prkar1a⁺; Rb1^tm2Brn/Rb1⁺; Tg(Col1a1-cre)1Kry/0; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129 * 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:234128 )

• mice survive to around 13.9 weeks

• treatment of mice with RANK-Fc prolongs survival to around 17.8 weeks

neoplasm

increased osteosarcoma incidence ( J:234128 )

• mice develop osteosarcoma within 10.3 weeks of age

• tumors are marked by high TNFSF11 (RANKL)/low TNFRSF11A (RANK) levels

• treatment of mice with RANK-Fc for 52 weeks beginning at 12.6 weeks of age keeps mice tumor-free until 64.6 weeks of age

skeleton

increased osteosarcoma incidence ( J:234128 )

• mice develop osteosarcoma within 10.3 weeks of age

• tumors are marked by high TNFSF11 (RANKL)/low TNFRSF11A (RANK) levels

• treatment of mice with RANK-Fc for 52 weeks beginning at 12.6 weeks of age keeps mice tumor-free until 64.6 weeks of age

cellular

increased cell migration ( J:234128 )

• in a scratch wound healing assay, tumor cells show greater migration than tumor cells from conditional Rb1^tm2Brn heterozygous Trp53^tm1Brn homozygous double mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteosarcoma		DOID:3347	OMIM:259500	J:234128

Genotype
MGI:5796167

cn10

• Allelic Composition: Prkar1a^tm1.2Lsk/Prkar1a⁺; Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Col1a1-cre)1Kry/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:234128 )

• mice do not live longer than 11 weeks

• treatment of mice with RANK-Fc prolongs survival to around to around 13.3 weeks

neoplasm

increased osteosarcoma incidence ( J:234128 )

• mice develop osteosarcoma within 6.3 weeks of age

• tumors are marked by high (TNFSF11) RANKL/low (TNFRSF11A) RANK levels

• treatment of mice with RANK-Fc starting at 2.4 weeks of age suppresses tumor growth

• mice develop tumors 4.3 weeks after the discontinuation of RANK-Fc treatment and large numbers of osteoclasts are seen lining the boundary of tumor cells and adjacent osteopetrotic bone

skeleton

increased osteosarcoma incidence ( J:234128 )

• mice develop osteosarcoma within 6.3 weeks of age

• tumors are marked by high (TNFSF11) RANKL/low (TNFRSF11A) RANK levels

• treatment of mice with RANK-Fc starting at 2.4 weeks of age suppresses tumor growth

• mice develop tumors 4.3 weeks after the discontinuation of RANK-Fc treatment and large numbers of osteoclasts are seen lining the boundary of tumor cells and adjacent osteopetrotic bone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteosarcoma		DOID:3347	OMIM:259500	J:234128

Genotype
MGI:5460854

cn11

• 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:5563247

cn12

• Allelic Composition: Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^tm1Sor; Pten^tm1Mro/Pten^tm1Mro; Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129 * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * FVB/N

neoplasm

increased nervous system tumor incidence ( J:204385 )

• mice injected with an adenovirus expressing cre (adeno-cre) into the lateral ventricle predominantly develop poorly differentiated, well-circumscribed neoplasms with similarity to supratentorial primitive neuroectodermal tumors (sPNET)

• expression profiles of tumors resemble human atypical teratoid/rhabdoid tumor

nervous system

increased nervous system tumor incidence ( J:204385 )

• mice injected with an adenovirus expressing cre (adeno-cre) into the lateral ventricle predominantly develop poorly differentiated, well-circumscribed neoplasms with similarity to supratentorial primitive neuroectodermal tumors (sPNET)

• expression profiles of tumors resemble human atypical teratoid/rhabdoid tumor

Genotype
MGI:5563244

cn13

• Allelic Composition: Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^tm1Sor; Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129 * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * FVB/N

neoplasm

increased nervous system tumor incidence ( J:204385 )

• mice injected with an adenovirus expressing cre (adeno-cre) into the lateral ventricle predominantly develop poorly differentiated, well-circumscribed neoplasms with similarity to supratentorial primitive neuroectodermal tumors (sPNET)

• expression profiles of tumors resemble human atypical teratoid/rhabdoid tumor

nervous system

increased nervous system tumor incidence ( J:204385 )

• mice injected with an adenovirus expressing cre (adeno-cre) into the lateral ventricle predominantly develop poorly differentiated, well-circumscribed neoplasms with similarity to supratentorial primitive neuroectodermal tumors (sPNET)

• expression profiles of tumors resemble human atypical teratoid/rhabdoid tumor

Genotype
MGI:7484008

cn14

• Allelic Composition: Dlg2^{tm1a(EUCOMM)Wtsi}/Dlg2^{tm1a(EUCOMM)Wtsi}; Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Col1a1-cre)1Kry/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6N * FVB/N
• Cell Lines: EPD0635_5_E12

mortality/aging

premature death ( J:269943 )

• mice exhibit a shortened overall survival, with a median lifespan of 184 days versus 239 days in control littermates that are wild-type for Dlg2

neoplasm

increased tumor growth/size ( J:269943 )

• tumor cells are more proliferative than those in control littermates that are wild-type for Dlg2, as indicated by Ki-67 staining

increased osteosarcoma incidence ( J:269943 )

• mice show accelerated osteosarcoma development with anatomical distribution and histological features similar to those in control littermates that are wild-type for Dlg2

• osteoblastic tumors are aggressive in nature, as indicated by abundant osteoid deposition at the invasive front of thoracic vertebra osteosarcomas

• plump tumorous osteoblasts and massive osteoid deposition are seen in tumors that develop at different sites

decreased tumor latency ( J:269943 )

• at 22 weeks of age, mice show accelerated tumor onset with visible signs of osteosarcomas on the tibia and ribs, unlike control littermates that are wild-type for Dlg2

skeleton

increased osteosarcoma incidence ( J:269943 )

• mice show accelerated osteosarcoma development with anatomical distribution and histological features similar to those in control littermates that are wild-type for Dlg2

• osteoblastic tumors are aggressive in nature, as indicated by abundant osteoid deposition at the invasive front of thoracic vertebra osteosarcomas

• plump tumorous osteoblasts and massive osteoid deposition are seen in tumors that develop at different sites

Genotype
MGI:5460840

cn15

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

mortality/aging

postnatal lethality ( J:190366 )

• death within 6-7 months of tamoxifen treatment

respiratory system

increased lung small cell carcinoma incidence ( J:190366 )

• small cell lung tumors 5-6 months after tamoxifen treatment in 4 of 32 mice examined, all with pulmonary neuroendocrine cells hyperplasia as well

abnormal pulmonary neuroendocrine body morphology ( J:190366 )

• pulmonary neuroendocrine cells hyperplasia 5-6 months after tamoxifen treatment in 16 of 32 mice examined

• increased proliferation of pulmonary neuroendocrine cells

neoplasm

increased thyroid tumor incidence ( J:190366 )

• all mice develop thyroid tumors

increased lung small cell carcinoma incidence ( J:190366 )

• small cell lung tumors 5-6 months after tamoxifen treatment in 4 of 32 mice examined, all with pulmonary neuroendocrine cells hyperplasia as well

endocrine/exocrine glands

increased thyroid tumor incidence ( J:190366 )

• all mice develop thyroid tumors

Genotype
MGI:5437518

cn16

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Gfap-cre)2Brn/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * FVB/N

neoplasm

increased pituitary gland tumor incidence ( J:187257 )

increased medulloblastoma incidence ( J:187257 )

increased carcinoma incidence ( J:187257 )

• large cell carcinoma

increased papilloma incidence ( J:187257 )

• choroid plexus papilloma

nervous system

increased pituitary gland tumor incidence ( J:187257 )

increased medulloblastoma incidence ( J:187257 )

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:187257 )

Genotype
MGI:5796161

cn17

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Col1a1-cre)1Kry/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * FVB/N

mortality/aging

premature death ( J:234128 )

• mice survive up to 38.1 weeks of age

neoplasm

increased osteosarcoma incidence ( J:234128 )

• mice develop osteosarcoma by 20 weeks of age

skeleton

increased osteosarcoma incidence ( J:234128 )

• mice develop osteosarcoma by 20 weeks of age

Genotype
MGI:5796164

cn18

• Allelic Composition: Rb1^tm2Brn/Rb1⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Col1a1-cre)1Kry/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * FVB/N

mortality/aging

premature death ( J:234128 )

• mice survive up to 55.4 weeks of age

neoplasm

increased osteosarcoma incidence ( J:234128 )

• mice develop osteosarcoma by 35 weeks of age

• tumors are marked by low TNFSF11 (RANKL)/high TNFRSF11A (RANK) levels

skeleton

increased osteosarcoma incidence ( J:234128 )

• mice develop osteosarcoma by 35 weeks of age

• tumors are marked by low TNFSF11 (RANKL)/high TNFRSF11A (RANK) levels

Genotype
MGI:7482566

cn19

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(BGLAP-cre)1Clem/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * FVB/NJ

mortality/aging

decreased tumor-free survival time ( J:326989 )

• tumor-free survival is 146.5 days

neoplasm

increased osteosarcoma incidence ( J:326989 )

• 52.4% incidence

skeleton

increased osteosarcoma incidence ( J:326989 )

• 52.4% incidence

Genotype
MGI:7277819

cn20

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-MYCN,-luc)Jhsc}/Gt(ROSA)26Sor⁺; Pten^tm2.1Ppp/Pten^tm2.1Ppp; Rb1^tm2Brn/Rb1^tm2Brn; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2

mortality/aging

premature death ( J:307910 )

♂ • median survival time of 12.5 weeks

♂ • castrated mice have a median survival time of 24 weeks

neoplasm

increased prostate gland tumor incidence ( J:307910 )

♂ • mice develop large, invasive prostate tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 8 weeks

♂ • these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states

♂ • some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

♂ • tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time

♂ • mice do not respond to surgical castration and continue to grow tumors rapidly

♂ • post-castration tumors harbor foci enriched with divergent differentiated histology compared to adenocarcinoma and increased metastatic potential

increased metastatic potential ( J:307910 )

♂ • onset of metastasis occurs as early as 8 weeks and by 12 weeks, 100% of mice develop distant metastatic lesions; metastases to the lung, liver, lymph nodes, and kidney primarily consist of large and small cell neuroendocrine histologies that are AR-negative

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:307910 )

♂ • mice develop large, invasive prostate tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 8 weeks

♂ • these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states

♂ • some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

♂ • tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time

♂ • mice do not respond to surgical castration and continue to grow tumors rapidly

♂ • post-castration tumors harbor foci enriched with divergent differentiated histology compared to adenocarcinoma and increased metastatic potential

reproductive system

increased prostate gland tumor incidence ( J:307910 )

♂ • mice do not respond to surgical castration and continue to grow tumors rapidly

♂ • mice develop large, invasive prostate tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 8 weeks

♂ • these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states

♂ • some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

♂ • tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time

♂ • post-castration tumors harbor foci enriched with divergent differentiated histology compared to adenocarcinoma and increased metastatic potential

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate neuroendocrine neoplasm		DOID:2992		J:307910

Genotype
MGI:7277820

cn21

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-MYCN,-luc)Jhsc}/Gt(ROSA)26Sor⁺; Pten^tm2.1Ppp/Pten^tm2.1Ppp; Rb1^tm2Brn/Rb1⁺; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2

mortality/aging

premature death ( J:307910 )

♂ • median survival time of 19 weeks

neoplasm

increased prostate gland tumor incidence ( J:307910 )

♂ • mice develop large, invasive tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 12 weeks

♂ • these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states

♂ • some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

♂ • tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:307910 )

♂ • mice develop large, invasive tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 12 weeks

♂ • these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states

♂ • some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

♂ • tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time

reproductive system

increased prostate gland tumor incidence ( J:307910 )

♂ • mice develop large, invasive tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 12 weeks

♂ • these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states

♂ • some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

♂ • tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate neuroendocrine neoplasm		DOID:2992		J:307910

Genotype
MGI:7277828

cn22

• Allelic Composition: Pten^tm2.1Ppp/Pten^tm2.1Ppp; Rb1^tm2Brn/Rb1^tm2Brn; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2

mortality/aging

premature death ( J:307910 )

• median survival time of 38 weeks

• castrated mice have a median survival time of 43.5 weeks

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:307910 )

• prostates from 8-week-old mice are composed of androgen receptor-positive, high-grade prostatic intraepithelial neoplasia lesions

• tumors regress post-castration but resume growth 24 weeks post-castration

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:307910 )

• prostates from 8-week-old mice are composed of androgen receptor-positive, high-grade prostatic intraepithelial neoplasia lesions

• tumors regress post-castration but resume growth 24 weeks post-castration

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:307910 )

• prostates from 8-week-old mice are composed of androgen receptor-positive, high-grade prostatic intraepithelial neoplasia lesions

• tumors regress post-castration but resume growth 24 weeks post-castration

Genotype
MGI:5789748

cn23

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Rbl1^tm1Tyj/Rbl1^tm1Tyj; Rbl2^tm2Tyj/Rbl2^tm2Tyj
• Genetic Background: involves: 129 * 129S2/SvPas * 129S4/SvJae

neoplasm

increased urinary bladder carcinoma incidence ( J:217195 )

• mice injected with an adenovirus expressing cre-recombinase (AdCre) into the bladder lumen all develop bladder lesions that resemble high-grade non-muscle-invasive carcinoma

• bladder tumors display high proliferation and invade the basal lamina

• metastases are not seen for up to 1 year after AdCre infection

renal/urinary system

hematuria ( J:217195 )

• hematuria is sometimes seen in mice injected with AdCre into the bladder lumen with bladder lesions

increased urinary bladder carcinoma incidence ( J:217195 )

• mice injected with an adenovirus expressing cre-recombinase (AdCre) into the bladder lumen all develop bladder lesions that resemble high-grade non-muscle-invasive carcinoma

• bladder tumors display high proliferation and invade the basal lamina

• metastases are not seen for up to 1 year after AdCre infection

homeostasis/metabolism

hematuria ( J:217195 )

• hematuria is sometimes seen in mice injected with AdCre into the bladder lumen with bladder lesions

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
urinary bladder cancer		DOID:11054	OMIM:109800	J:217195

Genotype
MGI:3710679

cn24

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Rbl2^tm1Tyj/Rbl2^tm1Tyj; Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds
• Genetic Background: involves: 129 * 129S2/SvPas * FVB/N

mortality/aging

premature death ( J:97589 )

• 36% die suddenly by 12 weeks of age and only 48% survive to 6 months of age

cardiovascular system

increased myocardial fiber size ( J:97589 )

• cardiomyocytes have an increase in diameter and contain large, hyperchromatic nuclei

enlarged heart ( J:97589 )

• mutants exhibit a 3-fold increase in the heart weight-to-body weight ratio at 8 weeks of age but not in the neonatal time period

dilated heart left ventricle ( J:97589 )

• mutants surviving to 12 weeks of age show evidence of LV dilation

decreased heart left ventricle muscle contractility ( J:97589 )

• end-diastolic diameter and end-systolic diameter are increased and left ventricular fractional shortening and circumferential shortening velocity are decreased in mutants surviving to 12 seeks of age, indicating left ventricular systolic dysfunction

decreased heart rate ( J:97589 )

• seen in mutants surviving to 12 weeks of age

abnormal myocardial fiber physiology ( J:97589 )

• hearts exhibit persistent myocyte cycling

respiratory system

respiratory distress ( J:97589 )

• 36% develop signs of respiratory distress

homeostasis/metabolism

edema ( J:97589 )

• 36% develop signs of generalized edema

muscle

increased myocardial fiber size ( J:97589 )

• cardiomyocytes have an increase in diameter and contain large, hyperchromatic nuclei

decreased heart left ventricle muscle contractility ( J:97589 )

• end-diastolic diameter and end-systolic diameter are increased and left ventricular fractional shortening and circumferential shortening velocity are decreased in mutants surviving to 12 seeks of age, indicating left ventricular systolic dysfunction

growth/size/body

enlarged heart ( J:97589 )

• mutants exhibit a 3-fold increase in the heart weight-to-body weight ratio at 8 weeks of age but not in the neonatal time period

Genotype
MGI:5563246

cn25

• Allelic Composition: Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^tm1Sor; Pten^tm1Mro/Pten^tm1Mro; Rb1^tm2Brn/Rb1^tm2Brn
• Genetic Background: involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB

neoplasm

neoplasm ( J:204385 )

N • mice injected with an adenovirus expressing cre (adeno-cre) into the lateral ventricle do not develop tumors after up to 440 days

Genotype
MGI:2653661

cn26

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brd/Trp53⁺; Tg(Rbp3-cre)1Brn/0
• Genetic Background: involves: 129 * 129S7/SvEvBrd * C57BL/6 * FVB/N

neoplasm

abnormal tumor morphology ( J:77982 )

• loss of heterozygosity of Trp53 in the neuroendocrine tumors

increased tumor incidence ( J:77982 )

• develop pituitary gland and pineal gland tumors

• pinealoblastomas locally invade the brain

Genotype
MGI:3804216

cn27

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brd/Trp53^tm1Brd; Tg(Gfap-cre)2Brn/0
• Genetic Background: involves: 129 * 129S7/SvEvBrd * FVB/N

neoplasm

increased medulloblastoma incidence ( J:61961 )

• mutants develop highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma

• tumors are identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the cerebellar external granular layer cells during development

behavior/neurological

tremors ( J:61961 )

ataxia ( J:61961 )

impaired balance ( J:61961 )

• loss of balance

• mutants hold their heads to one side

abnormal gait ( J:61961 )

• gait is disturbed with ataxia

circling ( J:61961 )

nervous system

increased medulloblastoma incidence ( J:61961 )

• mutants develop highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma

• tumors are identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the cerebellar external granular layer cells during development

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:61961

Genotype
MGI:3639920

cn28

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(Pou4f3-cre)1Devet/0
• Genetic Background: involves: 129 * 129S/SvEv

behavior/neurological

impaired swimming ( J:109453 )

• at 3 and 6 months, mutants are unable to swim with their heads above water

circling ( J:109453 )

• at 3 and 6 months, mutants display moderate circling behavior

hearing/vestibular/ear

abnormal organ of Corti supporting cell proliferation ( J:109453 )

• at P17, cochlear supporting cells are proliferating but in wild-type no proliferation is occurring at this age

abnormal organ of Corti morphology ( J:109453 )

• in the basal turn, the tunnel of corti has collapsed in 6-week old animals

abnormal cochlear hair cell morphology ( J:109453 )

• at P1 cochlear hair cells are still undergoing proliferation but in wild-type no proliferation is occurring at this age

increased cochlear inner hair cell number ( J:109453 )

• more inner hair cells than wild-type

abnormal cochlear outer hair cell morphology ( J:109453 )

• many outer hair cells lack bundles; atypical bundles including ring-shaped bundles and 2 bundles within one hair cell are occasionally observed

increased cochlear outer hair cell number ( J:109453 )

• more outer hair cells than wild-type

cochlear hair cell degeneration ( J:109453 )

• total hair cell loss by 3 months of age

cochlear outer hair cell degeneration ( J:109453 )

• from P6 to P17, there is apoptosis in the outer hair cell region of the organ of corti

abnormal vestibular hair cell morphology ( J:109453 )

• at P17, utrical hair cells are proliferating but in wild-type no proliferation is occurring at this age

vestibular hair cell degeneration ( J:109453 )

• numbers of vestibular hair cells decrease from early postnatal to adult stages

• at P6, there are three to four layers of hair cells in the utricle, but at 3 months, only 1-2 layers remain

• by 6 months, there are thin and disorganized hair bundles in most hair cells in the utricles

deafness ( J:109453 )

• mice are profoundly deaf by 3 months of age when all hair cells are lost

abnormal vestibular system physiology ( J:109453 )

• at 3 and 6 months, mutants display moderate circling behavior and can not swim with their heads above water

• at 6 months, partial vestibular function remains in mutants with hair cell and behavioral abnormalities

nervous system

abnormal cochlear hair cell morphology ( J:109453 )

• at P1 cochlear hair cells are still undergoing proliferation but in wild-type no proliferation is occurring at this age

increased cochlear inner hair cell number ( J:109453 )

• more inner hair cells than wild-type

abnormal cochlear outer hair cell morphology ( J:109453 )

• many outer hair cells lack bundles; atypical bundles including ring-shaped bundles and 2 bundles within one hair cell are occasionally observed

increased cochlear outer hair cell number ( J:109453 )

• more outer hair cells than wild-type

cochlear hair cell degeneration ( J:109453 )

• total hair cell loss by 3 months of age

cochlear outer hair cell degeneration ( J:109453 )

• from P6 to P17, there is apoptosis in the outer hair cell region of the organ of corti

abnormal vestibular hair cell morphology ( J:109453 )

• at P17, utrical hair cells are proliferating but in wild-type no proliferation is occurring at this age

vestibular hair cell degeneration ( J:109453 )

• numbers of vestibular hair cells decrease from early postnatal to adult stages

• at P6, there are three to four layers of hair cells in the utricle, but at 3 months, only 1-2 layers remain

• by 6 months, there are thin and disorganized hair bundles in most hair cells in the utricles

cellular

abnormal organ of Corti supporting cell proliferation ( J:109453 )

• at P17, cochlear supporting cells are proliferating but in wild-type no proliferation is occurring at this age

Genotype
MGI:5468652

cn29

• Allelic Composition: Ccnd3^tm1Pisc/Ccnd3^tm1Pisc; Rb1^tm2Brn/Rb1^tm2Brn; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

immune system

decreased T cell proliferation ( J:192031 )

• of pre-T cells as in Ccnd3^tm1Pisc homozygotes

thymus hypoplasia ( J:192031 )

• not as severe as in pIpC-treated mice as in Ccnd3^tm1Pisc homozygotes

decreased double-positive T cell number ( J:192031 )

• as in Ccnd3^tm1Pisc homozygotes

hematopoietic system

decreased T cell proliferation ( J:192031 )

• of pre-T cells as in Ccnd3^tm1Pisc homozygotes

thymus hypoplasia ( J:192031 )

• not as severe as in pIpC-treated mice as in Ccnd3^tm1Pisc homozygotes

decreased double-positive T cell number ( J:192031 )

• as in Ccnd3^tm1Pisc homozygotes

endocrine/exocrine glands

thymus hypoplasia ( J:192031 )

• not as severe as in pIpC-treated mice as in Ccnd3^tm1Pisc homozygotes

cellular

decreased T cell proliferation ( J:192031 )

• of pre-T cells as in Ccnd3^tm1Pisc homozygotes

Genotype
MGI:5614112

cn30

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(Cyp1a1-cre)1Dwi/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

cellular

abnormal enterocyte proliferation ( J:215358 )

• increased proliferation of columnar epithelial cells of the villi

digestive/alimentary system

abnormal enterocyte proliferation ( J:215358 )

• increased proliferation of columnar epithelial cells of the villi

Genotype
MGI:3842836

cn31

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(KRT14-cre)8Brn/0; Tg(KRT5-Akt1*)Jmpa/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2 * DBA/2J * FVB/N

neoplasm

increased tumor incidence ( J:144831 )

• pathologic characteristics of oral lesions and tumor development rate are the same as in Tg(KRT5-Akt1*)Jmpa mice

craniofacial

abnormal oral mucosa morphology ( J:144831 )

• pathologic characteristics of oral lesions and tumor development rate are the same as in Tg(KRT5-Akt1*)Jmpa mice

digestive/alimentary system

abnormal oral mucosa morphology ( J:144831 )

• pathologic characteristics of oral lesions and tumor development rate are the same as in Tg(KRT5-Akt1*)Jmpa mice

growth/size/body

abnormal oral mucosa morphology ( J:144831 )

• pathologic characteristics of oral lesions and tumor development rate are the same as in Tg(KRT5-Akt1*)Jmpa mice

Genotype
MGI:3574808

cn32

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(Col1a1-cre)1Bek/0
• Genetic Background: involves: 129 * CD-1

mortality/aging

perinatal lethality ( J:96345 )

hearing/vestibular/ear

abnormal organ of Corti supporting cell proliferation ( J:96345 )

• detected many proliferating cochlear supporting cells at E13.5 and E18.5 when these cells are normally postmitotic, indicating that differentiated cells continue to cycle and divide

abnormal organ of Corti morphology ( J:96345 )

• proliferating cells were found in the zone of nonproliferating cells in the primordial organ of Corti at E13.5

increased cochlear hair cell number ( J:96345 )

• increased hair bundle number in E18.5 cochleas with many improperly oriented

• detected many proliferating hair cells at E13.5 and E18.5 when these cells are normally postmitotic, indicating that differentiated cells continue to cycle and divide

increased cochlear inner hair cell number ( J:96345 )

• cochleas had 3-4 rows of inner hair cells compared to one row of inner hair cells in wildtype

increased cochlear outer hair cell number ( J:96345 )

• cochleas had 7-8 rows of outer hair cells compared to 3 rows of outer hair cells in wildtype

increased Deiters cell number ( J:96345 )

• increased ratio of outer hair cells to Deiters' cells, suggesting continous hair cell division

• increased numbers of Deiters' cells, but not pillar cells, than in controls

increased vestibular hair cell number ( J:96345 )

• E18.5 utricles had 40% more cells with bundles

• proliferating hair cells and supporting cells were seen in the utricle at E13.5 and E18.5 when these cells are normally postmitotic, however, cell fate determination and subsequent differentiation was intact in these proliferating cells

• observed hair cells in metaphase in E18.5 utricles

abnormal hearing physiology ( J:96345 )

• transduction currents in ear hair cells were smaller than in controls (10-20 pA versus 200 pA in controls)

nervous system

increased cochlear hair cell number ( J:96345 )

• increased hair bundle number in E18.5 cochleas with many improperly oriented

• detected many proliferating hair cells at E13.5 and E18.5 when these cells are normally postmitotic, indicating that differentiated cells continue to cycle and divide

increased cochlear inner hair cell number ( J:96345 )

• cochleas had 3-4 rows of inner hair cells compared to one row of inner hair cells in wildtype

increased cochlear outer hair cell number ( J:96345 )

• cochleas had 7-8 rows of outer hair cells compared to 3 rows of outer hair cells in wildtype

increased vestibular hair cell number ( J:96345 )

• E18.5 utricles had 40% more cells with bundles

• proliferating hair cells and supporting cells were seen in the utricle at E13.5 and E18.5 when these cells are normally postmitotic, however, cell fate determination and subsequent differentiation was intact in these proliferating cells

• observed hair cells in metaphase in E18.5 utricles

cellular

abnormal organ of Corti supporting cell proliferation ( J:96345 )

• detected many proliferating cochlear supporting cells at E13.5 and E18.5 when these cells are normally postmitotic, indicating that differentiated cells continue to cycle and divide

Genotype
MGI:3710677

cn33

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds
• Genetic Background: involves: 129 * FVB

normal phenotype

no abnormal phenotype detected ( J:97589 )

• mutants are born with the expected Mendelian distribution and adult show no change in heart size, myocyte cell distribution, myocyte apoptosis, or mechanical function

Genotype
MGI:3804218

cn34

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(Gfap-cre)2Brn/0
• Genetic Background: involves: 129 * FVB/N

mortality/aging

premature death ( J:187257 )

neoplasm

neoplasm ( J:61961 )

N • mutants do not develop medulloblastomas

increased pituitary gland tumor incidence ( J:187257 )

increased carcinoma incidence ( J:187257 )

• large cell carcinoma

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:187257 )

nervous system

increased pituitary gland tumor incidence ( J:187257 )

Genotype
MGI:2653660

cn35

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(Rbp3-cre)1Brn/0
• Genetic Background: involves: 129 * FVB/N

neoplasm

increased pituitary adenohypophysis tumor incidence ( J:77982 )

• develop pituitary gland tumors that arise from the anterior lobe of the pituitary gland

• however, do not develop retinoblastomas or pineal gland tumors

increased pituitary melanotroph tumor incidence ( J:77982 )

• develop pituitary gland tumors that arise from the intermediate lobe of the pituitary gland

endocrine/exocrine glands

increased pituitary adenohypophysis tumor incidence ( J:77982 )

• develop pituitary gland tumors that arise from the anterior lobe of the pituitary gland

• however, do not develop retinoblastomas or pineal gland tumors

increased pituitary melanotroph tumor incidence ( J:77982 )

• develop pituitary gland tumors that arise from the intermediate lobe of the pituitary gland

vision/eye

vision/eye phenotype ( J:77982 )

N • retinas appear normal

nervous system

increased pituitary adenohypophysis tumor incidence ( J:77982 )

• develop pituitary gland tumors that arise from the anterior lobe of the pituitary gland

• however, do not develop retinoblastomas or pineal gland tumors

increased pituitary melanotroph tumor incidence ( J:77982 )

• develop pituitary gland tumors that arise from the intermediate lobe of the pituitary gland

Genotype
MGI:7482567

cn36

• Allelic Composition: Nell1^tm1Kuv/Nell1^tm1Kuv; Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(BGLAP-cre)1Clem/0
• Genetic Background: involves: 129 * FVB/NJ

mortality/aging

increased tumor-free survival time ( J:326989 )

• tumor-free survival is 398 days compared to 146.5 days in mutant mice wild-type for Nell1

neoplasm

abnormal tumor morphology ( J:326989 )

• 85.2% decrease in the proliferative-index in tumors compared to tumors in mutant mice wild-type for Nell1

abnormal tumor vascular morphology ( J:326989 )

• 66.1% decrease in tumor-associated vasculature compared to mutant mice wild-type for Nell1

decreased osteosarcoma incidence ( J:326989 )

• 15.8% incidence compared to 52.4% incidence in mutant mice wild-type for Nell1

skeleton

decreased osteosarcoma incidence ( J:326989 )

• 15.8% incidence compared to 52.4% incidence in mutant mice wild-type for Nell1

Genotype
MGI:5704166

cn37

• Allelic Composition: Rb1^tm2Brn/Rb1⁺; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd

neoplasm

abnormal tumor pathology ( J:86077 )

• some mice treated with a cre-expressing adenovirus exhibit metastasis in the mediastinum, ovary and adrenal gland

increased lung adenocarcinoma incidence ( J:86077 )

• in some mice treated with a cre-expressing adenovirus

increased lung small cell carcinoma incidence ( J:86077 )

• small in some mice treated with a cre-expressing adenovirus

respiratory system

increased lung adenocarcinoma incidence ( J:86077 )

• in some mice treated with a cre-expressing adenovirus

increased lung small cell carcinoma incidence ( J:86077 )

• small in some mice treated with a cre-expressing adenovirus

Genotype
MGI:4437461

cn38

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd

endocrine/exocrine glands

increased thyroid carcinoma incidence ( J:86077 , J:157319 )

• medullary thyroid carcinomas in some mice treated with a cre-expressing adenovirus (J:86077)

• following treatment with cre-expressing adenovirus, 6 of 33 mice develop medullary thyroid carcinoma unlike wild-type mice (J:157319)

increased ovary tumor incidence ( J:84345 )

♀ • after a single ovarian intrabursal injection of an adenovirus expressing Cre, mutant females develop epithelial ovarian cancer similar in progression of disease in women, with ovarian neoplasms spreading, forming ascites and metastasizing to the contralateral ovary, the lung and the liver

♀ • 39% are well-differentiated serous epithelial neoplasms of the ovary and 45% are poorly differentiated CK8-positive neoplasms of the ovary

increased ovarian carcinoma incidence ( J:84345 )

♀ • the ovarian cancer found after a single ovarian intrabursal injection of an adenovirus expressing Cre is characterisitic of serous adenocarcinoma

mortality/aging

decreased tumor-free survival time ( J:84345 )

• 97% of mice succumb to ovarian tumors at a median age of 227 days after after a single ovarian intrabusal injection of an adenovirus expressing Cre

neoplasm

increased thyroid carcinoma incidence ( J:86077 , J:157319 )

• medullary thyroid carcinomas in some mice treated with a cre-expressing adenovirus (J:86077)

• following treatment with cre-expressing adenovirus, 6 of 33 mice develop medullary thyroid carcinoma unlike wild-type mice (J:157319)

increased ovary tumor incidence ( J:84345 )

♀ • after a single ovarian intrabursal injection of an adenovirus expressing Cre, mutant females develop epithelial ovarian cancer similar in progression of disease in women, with ovarian neoplasms spreading, forming ascites and metastasizing to the contralateral ovary, the lung and the liver

♀ • 39% are well-differentiated serous epithelial neoplasms of the ovary and 45% are poorly differentiated CK8-positive neoplasms of the ovary

increased ovarian carcinoma incidence ( J:84345 )

♀ • the ovarian cancer found after a single ovarian intrabursal injection of an adenovirus expressing Cre is characterisitic of serous adenocarcinoma

abnormal tumor pathology ( J:86077 )

• various metastases in some mice treated with a cre-expressing adenovirus

increased metastatic potential ( J:84345 )

• 15% of tumors that form in females after a single ovarian intrabursal injection of an adenovirus expressing Cre metastasized to the opposite ovary, 18% of tumors metastasized to the lung, and 6% of tumors metastasized to the liver

increased lung tumor incidence ( J:157319 )

• mice treated with cre-expressing adenovirus median tumor-free survival is 210 days

increased lung carcinoma incidence ( J:86077 )

• bronchioalveolar carcinomas in some mice treated with a cre-expressing adenovirus

increased lung small cell carcinoma incidence ( J:86077 , J:157319 )

• mice treated with a cre-expressing adenovirus exhibit multiple dysplastic foci of clustering small cells in the bronchial and bronchiolar mucosa (J:86077)

• mice treated with cre-expressing adenovirus exhibit dysplastic foci of clustering small cells in the bronchial and bronchiolar mucosa unlike in wild-type mice (J:157319)

reproductive system

increased ovary tumor incidence ( J:84345 )

♀ • after a single ovarian intrabursal injection of an adenovirus expressing Cre, mutant females develop epithelial ovarian cancer similar in progression of disease in women, with ovarian neoplasms spreading, forming ascites and metastasizing to the contralateral ovary, the lung and the liver

♀ • 39% are well-differentiated serous epithelial neoplasms of the ovary and 45% are poorly differentiated CK8-positive neoplasms of the ovary

increased ovarian carcinoma incidence ( J:84345 )

♀ • the ovarian cancer found after a single ovarian intrabursal injection of an adenovirus expressing Cre is characterisitic of serous adenocarcinoma

respiratory system

increased lung tumor incidence ( J:157319 )

• mice treated with cre-expressing adenovirus median tumor-free survival is 210 days

increased lung carcinoma incidence ( J:86077 )

• bronchioalveolar carcinomas in some mice treated with a cre-expressing adenovirus

increased lung small cell carcinoma incidence ( J:86077 , J:157319 )

• mice treated with a cre-expressing adenovirus exhibit multiple dysplastic foci of clustering small cells in the bronchial and bronchiolar mucosa (J:86077)

• mice treated with cre-expressing adenovirus exhibit dysplastic foci of clustering small cells in the bronchial and bronchiolar mucosa unlike in wild-type mice (J:157319)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lung small cell carcinoma		DOID:5409	OMIM:182280	J:157319 , J:86077
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:84345

Genotype
MGI:4437462

cn39

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53⁺
• Genetic Background: involves: 129P2/OlaHsd

neoplasm

increased thyroid carcinoma incidence ( J:86077 , J:157319 )

• medullary thyroid carcinomas in 2 of 13 mice treated with a cre-expressing adenovirus (J:86077)

• following treatment with cre-expressing adenovirus, 2 of 13 mice exhibit medullary thyroid carcinoma unlike wild-type mice (J:157319)

increased lung tumor incidence ( J:157319 )

• mice treated with cre-expressing adenovirus median tumor-free survival is 475 days

increased lung adenocarcinoma incidence ( J:86077 , J:157319 )

• in some mice treated with a cre-expressing adenovirus (J:86077)

• in some mice following treatment with cre-expressing adenovirus (J:157319)

increased lung small cell carcinoma incidence ( J:86077 , J:157319 )

• large in 5 of 13 mice treated with a cre-expressing adenovirus (J:86077)

• in some mice following treatment with cre-expressing adenovirus (J:157319)

endocrine/exocrine glands

increased thyroid carcinoma incidence ( J:86077 , J:157319 )

• medullary thyroid carcinomas in 2 of 13 mice treated with a cre-expressing adenovirus (J:86077)

• following treatment with cre-expressing adenovirus, 2 of 13 mice exhibit medullary thyroid carcinoma unlike wild-type mice (J:157319)

respiratory system

increased lung tumor incidence ( J:157319 )

• mice treated with cre-expressing adenovirus median tumor-free survival is 475 days

increased lung adenocarcinoma incidence ( J:86077 , J:157319 )

• in some mice treated with a cre-expressing adenovirus (J:86077)

• in some mice following treatment with cre-expressing adenovirus (J:157319)

increased lung small cell carcinoma incidence ( J:86077 , J:157319 )

• large in 5 of 13 mice treated with a cre-expressing adenovirus (J:86077)

• in some mice following treatment with cre-expressing adenovirus (J:157319)

Genotype
MGI:3710239

cn40

• Allelic Composition: Rb1^tm1Tyj/Rb1^tm2Brn; Rbl1^tm1Tyj/Rbl1^tm1Tyj; Trp53^tm1Brn/Trp53^tm1Tyj; Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL

vision/eye

increased retinoblastoma incidence ( J:120315 )

• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites

• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber

abnormal eye anterior chamber morphology ( J:120315 )

• tumor cells that invade the anterior eye chamber beneath the cornea are densely packed stage II cells surrounded by sparse regions of plexus with no synaptic densities or vesiclesin in the plexus or rosettes of these cells

• tumor cells have abundant mitochondria and mitotic figures; some rosettes have a central plexus made up of large, undifferentiated processes, with other rosettes having a central plexus containing neurons and synapses

abnormal eye posterior chamber morphology ( J:120315 )

• areas of the plexus within the posterior chamber are composed of neuron-like processes having synaptic structures similar to horizontal/amacrine cells; this is seen in extensive plexus areas of tumors

neoplasm

increased retinoblastoma incidence ( J:120315 )

• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites

• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber

cellular

abnormal cell proliferation ( J:120315 )

• a substantial proportion of tumor cells expressing amacrine/horizontal cell markers are proliferating as shown by labeled thymidine incorporation

Genotype
MGI:3710238

cn41

• Allelic Composition: Rb1^tm1Tyj/Rb1^tm2Brn; Rbl1^tm1Tyj/Rbl1^tm1Tyj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL

vision/eye

abnormal eye anterior chamber morphology ( J:120315 )

• tumor cells that invade the anterior eye chamber beneath the cornea are densely packed stage II cells surrounded by sparse regions of plexus with no synaptic densities or vesiclesin in the plexus or rosettes of these cells

• tumor cells have abundant mitochondria and mitotic figures; some rosettes have a central plexus made up of large, undifferentiated processes, with other rosettes having a central plexus containing neurons and synapses

abnormal eye posterior chamber morphology ( J:120315 )

• areas of the plexus within the posterior chamber are composed of neuron-like processes having synaptic structures similar to horizontal/amacrine cells; this is seen in smaller areas of plexus in tumors

• processes are usually smaller in diameter (<0.5 um) but large ones of 1-3 um are observed occasionally; variety of synaptic arrangements occur and all types can be found in contacts among processes, while ribbon synapses are seen only in areas near photoreceptor cell bodies

abnormal retina morphology ( J:120315 )

• significant disruptions in retinal morphology are observed by P12 to 13

• in diseased eyes, retina blastoma cells rupture the inner limiting membrane (ILM), particularly by the apex of vitreal protrusions that may be present; at these points, tumor cell bodies and associated vasculature can be seen

increased retinoblastoma incidence ( J:120315 )

• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants; tumor size varies with age and genotype

• an early-stage tumor displayed a pronounced vitreal protrusion in one animal, and contained structures resembling neuronal processes like those in the plexiform layer of the normal retina

• in tumors, proteins usually found in amacrine/horizontal cells, including Gad65, Snap25, Calbindin, vGlut-1, E-cadherin, N-cadherin, synapsin, and Syntaxin-1 are expressed; these cells are considered to be differentiated

• cells positive for amacrine/horizontal cell markers (1.7-3.6 x 10⁶ cells/tumor) are much more numerous than number of amacrine/horizontal cells in a normal retina

• regions of tumors negative for amacrine/horizontal markers contain more densely packed nuclei

neoplasm

increased retinoblastoma incidence ( J:120315 )

• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants; tumor size varies with age and genotype

• an early-stage tumor displayed a pronounced vitreal protrusion in one animal, and contained structures resembling neuronal processes like those in the plexiform layer of the normal retina

• in tumors, proteins usually found in amacrine/horizontal cells, including Gad65, Snap25, Calbindin, vGlut-1, E-cadherin, N-cadherin, synapsin, and Syntaxin-1 are expressed; these cells are considered to be differentiated

• cells positive for amacrine/horizontal cell markers (1.7-3.6 x 10⁶ cells/tumor) are much more numerous than number of amacrine/horizontal cells in a normal retina

• regions of tumors negative for amacrine/horizontal markers contain more densely packed nuclei

Genotype
MGI:3710241

cn42

• Allelic Composition: Rb1^tm1Tyj/Rb1^tm2Brn; Rbl1^tm1Tyj/Rbl1⁺; Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL

nervous system

decreased retina photoreceptor cell number ( J:120315 )

• mice with retinoblastoma tumors are characterized by pronounced loss of photoreceptor cells

neoplasm

increased retinoblastoma incidence ( J:120315 )

• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites

• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber

• tumors show appearance of unique populations of undifferentiated tumor-like cells, and extensive formation of plexiform regions

• in a large tumor that filled much of the vitreal space contained two cell types: some cells are stage I retinoblastoma cells with pale, round nuclei resembling differentiated neurons and always associated with a plexus or tightly-packed stage II retinoblastoma cells with irregular nuclei with little or no plexus associated with individual cells

• rosettes in retinoblastomas are usually composed of stage I cells with a central plexus, but are adjacent to clusters of stage II cells

• plexus regions of tumors show mitotic figures and apoptotic cells; plexus regions also contained synaptic densities and associated synaptic vesicles

vision/eye

abnormal eye posterior chamber morphology ( J:120315 )

• areas of the plexus within the posterior chamber are composed of neuron-like processes having synaptic structures similar to horizontal/amacrine cells; this is seen in smaller areas of plexus in tumors

• processes are usually smaller in diameter (<0.5 um) but large ones of 1-3 um are observed occasionally; variety of synaptic arrangements occur and all types can be found in contacts among processes, while ribbon synapses are seen only in areas near photoreceptor cell bodies

abnormal retina morphology ( J:120315 )

• significant disruptions in retinal morphology are observed by P12 to 13

increased retinoblastoma incidence ( J:120315 )

• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites

• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber

• tumors show appearance of unique populations of undifferentiated tumor-like cells, and extensive formation of plexiform regions

• in a large tumor that filled much of the vitreal space contained two cell types: some cells are stage I retinoblastoma cells with pale, round nuclei resembling differentiated neurons and always associated with a plexus or tightly-packed stage II retinoblastoma cells with irregular nuclei with little or no plexus associated with individual cells

• rosettes in retinoblastomas are usually composed of stage I cells with a central plexus, but are adjacent to clusters of stage II cells

• plexus regions of tumors show mitotic figures and apoptotic cells; plexus regions also contained synaptic densities and associated synaptic vesicles

decreased retina photoreceptor cell number ( J:120315 )

• mice with retinoblastoma tumors are characterized by pronounced loss of photoreceptor cells

Genotype
MGI:3710240

cn43

• Allelic Composition: Rb1^tm1Tyj/Rb1^tm2Brn; Rbl1^tm1Tyj/Rbl1⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL

vision/eye

abnormal retina morphology ( J:120315 )

• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants, but onset is delayed compared to that observed in Rbl1 homozygous compound mutants

• tumor size varies with age and genotype

• mice show rapid filling of the vitreal cavity with densely packed tumor cells and rosettes; in the tumors, there is an overabundance of stage II retinoblastoma cells

• near outer surface of retina near tumor origin site, there are regions of plexus with synaptic densities and synaptic vesicles, indistinguishable from the Rb1;Rbl1 mutants that are wild-type for Trp53

increased retinoblastoma incidence ( J:120315 )

• significant disruptions in retinal morphology are observed by P12 to 13

neoplasm

increased retinoblastoma incidence ( J:120315 )

• significant disruptions in retinal morphology are observed by P12 to 13

Genotype
MGI:3707498

cn44

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Rbl1^tm1Htr/Rbl1^tm1Htr; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd * CD-1

behavior/neurological

ataxia ( J:83783 )

• mutants develop ataxia between P15 and P20

nervous system

abnormal neuronal precursor proliferation ( J:83783 )

• increased proliferation is even more pronounced in cerebella of mutants at P15 and 20

abnormal cerebellar cortex morphology ( J:83783 )

• at P20, mice have highly disorganized cerebellar architecture in median cerebellar region

abnormal Purkinje cell morphology ( J:83783 )

• dendritic arborization appears shrunken, with stunted to misoriented dendrites

• cell bodies are poorly aligned with loss of laminar distribution

• occasionally bi-nucleated neurons are observed

thin cerebellar molecular layer ( J:83783 )

• layer is reduce in size

abnormal cerebellum vermis morphology ( J:83783 )

• at P15, the vermis is severely reduced in size

cellular

abnormal neuronal precursor proliferation ( J:83783 )

• increased proliferation is even more pronounced in cerebella of mutants at P15 and 20

Genotype
MGI:3707502

cn45

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Rbl1^tm1Htr/Rbl1⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd * CD-1

cellular

cellular phenotype ( J:83783 )

N • mice have similar levels of apoptosis in the cerebella as Rb1, Rbl1 double mutants which express Trp53

Genotype
MGI:3707499

cn46

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Rbl1^tm1Htr/Rbl1⁺; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd * CD-1

behavior/neurological

ataxia ( J:83783 )

• mutants develop ataxia between P15 and P20

nervous system

increased neuron apoptosis ( J:83783 )

• increase in apoptotic rate is seen at P15 in vermis of mutants; most apoptotic cells are found in the inner half of the external granule layer and in the inner granule layer; rate is similar at P30

abnormal neuronal precursor proliferation ( J:83783 )

• at P15, number of proliferating granule cell precursors in external granule layer is higher than in controls

abnormal cerebellum vermis morphology ( J:83783 )

• at P15, the vermis is considerably reduced in size, but less than when both Rbl1 alleles are lost

cerebellum hypoplasia ( J:83783 )

• at P15, size reduction compared to wild-type cerebella is noticed

cellular

increased neuron apoptosis ( J:83783 )

• increase in apoptotic rate is seen at P15 in vermis of mutants; most apoptotic cells are found in the inner half of the external granule layer and in the inner granule layer; rate is similar at P30

abnormal neuronal precursor proliferation ( J:83783 )

• at P15, number of proliferating granule cell precursors in external granule layer is higher than in controls

Genotype
MGI:3707497

cn47

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd * CD-1

nervous system

increased neuron apoptosis ( J:83783 )

• increase in apoptotic rate is seen at P15 in vermis of mutants; most apoptotic cells are found in the inner half of the external granule layer and in the inner granule layer; rate is similar at P30 and is accelerated compared to Rb1 single mutant mice

• there is no detectable Purkinje cell apoptosis

abnormal neuronal precursor proliferation ( J:83783 )

• at P15, number of proliferating granule cell precursors in cerebellum is higher than in controls; at P20, proliferation in external granule layer (EGL) of vermis is increased while in the internal granule layer (IGL), higher proliferation is detected at P8

abnormal cerebellum external granule cell layer morphology ( J:83783 )

• at P 15, thickness of the external granule layer (EGL) is greater (4-5 cells thick) relative to wild-type (1 or 2 cells thick)

thin external granule cell layer ( J:83783 )

• at P20, mice have a persisten thin EGL with granule cell precursors still migrating through the molecular layer

abnormal brain interneuron morphology ( J:83783 )

• interneurons of molecular layer of cerebellum are substantially reduced in number at P20, which is most pronounced in lobules VI and VII

abnormal cerebellar cortex morphology ( J:83783 )

• numbers of granule, basket and stellate neurons are considerably reduced compared to wild-type

abnormal Purkinje cell morphology ( J:83783 )

• Purkinje cells are slightly irregularly arranged and have moderately enlarged somata and nuclei

• Purkinje cells in vermis appear disarranged, and occasionally show enlarged nuclei with abnormal shapes and reduced dendritic arborization

abnormal cerebellar granule layer morphology ( J:83783 )

• thickness and cellularity of the internal granule layer (IGL ) is reduced at P20 compared to wild-type; this is most pronounced in lobules VI and VII

abnormal cerebellar granule cell morphology ( J:83783 )

• numbers are severely reduced in cerebellum

astrocytosis ( J:83783 )

• a brisk widespread astrogliosis in observed in the IGL

cellular

increased neuron apoptosis ( J:83783 )

• increase in apoptotic rate is seen at P15 in vermis of mutants; most apoptotic cells are found in the inner half of the external granule layer and in the inner granule layer; rate is similar at P30 and is accelerated compared to Rb1 single mutant mice

• there is no detectable Purkinje cell apoptosis

abnormal neuronal precursor proliferation ( J:83783 )

• at P15, number of proliferating granule cell precursors in cerebellum is higher than in controls; at P20, proliferation in external granule layer (EGL) of vermis is increased while in the internal granule layer (IGL), higher proliferation is detected at P8

Genotype
MGI:3707500

cn48

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Rbl1^tm1Htr/Rbl1^tm1Htr; Tg(Pcp2-cre)756Mro/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

nervous system

abnormal Purkinje cell morphology ( J:83783 )

• some Purkinje cells show enlarged nuclei with abnormal hourglass or kidney shapes

Genotype
MGI:3707501

cn49

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(Pcp2-cre)756Mro/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

nervous system

abnormal cerebellum vermis morphology ( J:83783 )

• at P15, the vermis is considerably reduced in size, but less than when both Rbl1 alleles are lost

Genotype
MGI:3804217

cn50

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Gfap-cre)2Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

neoplasm

increased medulloblastoma incidence ( J:61961 )

• mutants develop medulloblastomas

nervous system

increased medulloblastoma incidence ( J:61961 )

• mutants develop medulloblastomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:61961

Genotype
MGI:5468653

cn51

• Allelic Composition: Ccnd3^tm1Pisc/Ccnd3^tm1Pisc; Cdkn1b^tm1Mlf/Cdkn1b^tm1Mlf; Rb1^tm2Brn/Rb1^tm2Brn; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6 * CBA

immune system

immune system phenotype ( J:192031 )

N • mice exhibit normal numbers of thymocytes, double negative cells, double positive cells and pre-T cell proliferation

Genotype
MGI:3618365

cn52

• Allelic Composition: Rb1^tm1Dwg/Rb1^tm2Brn; Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
• Genetic Background: involves: 129/Sv * C57BL/6 * SJL

vision/eye

decreased retina rod cell number ( J:105548 )

• significant reduction in rod photoreceptors at P14, however no changes in the number of other major cell types in the retina

abnormal retina horizontal cell morphology ( J:105548 )

• horizontal cell synaptogenesis in the retina is defective

nervous system

decreased retina rod cell number ( J:105548 )

• significant reduction in rod photoreceptors at P14, however no changes in the number of other major cell types in the retina

abnormal retina horizontal cell morphology ( J:105548 )

• horizontal cell synaptogenesis in the retina is defective