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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Rb1tm2Brn
targeted mutation 2, Anton Berns
MGI:1931018
Summary 52 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Rb1tm2Brn/Rb1tm2Brn involves: 129 MGI:4437463
cn2
Rb1tm2Brn/Rb1tm2Brn involves: 129 * BALB/c MGI:4353993
cn3
Gt(ROSA)26Sortm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor+
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Gfap-cre)2Brn/0
either: (involves: 129 * 129P2/OlaHsd * FVB/N) or (involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB/N) MGI:5437517
cn4
Gt(ROSA)26Sortm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor+
Rb1tm2Brn/Rb1tm2Brn
Tg(Gfap-cre)2Brn/0
either: (involves: 129 * 129P2/OlaHsd * FVB/N) or (involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB/N) MGI:5437516
cn5
Rb1tm2Brn/Rb1tm2Brn
Tg(MMTV-cre)105Ayn/0
FVB.Cg-Rb1tm2Brn Tg(MMTV-cre)105Ayn MGI:4837143
cn6
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(MMTV-cre)105Ayn/0
FVB.Cg-Trp53tm1Brn Rb1tm2Brn Tg(MMTV-cre)105Ayn MGI:4837145
cn7
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Lejo/Trp53tm1Lejo
involves: 129 MGI:5441551
cn8
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Ren-cre)#Kwg/0
involves: 129 * 129P2/OlaHsd MGI:5662454
cn9
Prkar1atm1.2Lsk/Prkar1a+
Rb1tm2Brn/Rb1+
Tg(Col1a1-cre)1Kry/0
Trp53tm1Brn/Trp53tm1Brn
involves: 129 * 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB/N MGI:5796166
cn10
Prkar1atm1.2Lsk/Prkar1a+
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Col1a1-cre)1Kry/0
involves: 129 * 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB/N MGI:5796167
cn11
Calcatm1.1(cre/ERT2)Ptch/Calca+
Trp53tm1Brn/Trp53tm1Brn
Rb1tm2Brn/Rb1tm2Brn
Ptentm1Hwu/Ptentm1Hwu
involves: 129 * 129P2/OlaHsd * 129S4/SvJae * BALB/c * FVB/N MGI:5460854
cn12
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sortm1Sor
Ptentm1Mro/Ptentm1Mro
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
involves: 129 * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * FVB/N MGI:5563247
cn13
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sortm1Sor
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
involves: 129 * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * FVB/N MGI:5563244
cn14
Dlg2tm1a(EUCOMM)Wtsi/Dlg2tm1a(EUCOMM)Wtsi
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Col1a1-cre)1Kry/0
involves: 129 * 129P2/OlaHsd * C57BL/6N * FVB/N MGI:7484008
cn15
Rb1tm2Brn/Rb1+
Trp53tm1Brn/Trp53tm1Brn
Tg(Col1a1-cre)1Kry/0
involves: 129 * 129P2/OlaHsd * FVB/N MGI:5796164
cn16
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Gfap-cre)2Brn/0
involves: 129 * 129P2/OlaHsd * FVB/N MGI:5437518
cn17
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Col1a1-cre)1Kry/0
involves: 129 * 129P2/OlaHsd * FVB/N MGI:5796161
cn18
Calcatm1.1(cre/ERT2)Ptch/Calca+
Trp53tm1Brn/Trp53tm1Brn
Rb1tm2Brn/Rb1tm2Brn
involves: 129 * 129P2/OlaHsd * FVB/N MGI:5460840
cn19
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(BGLAP-cre)1Clem/0
involves: 129 * 129P2/OlaHsd * FVB/NJ MGI:7482566
cn20
Gt(ROSA)26Sortm1(CAG-MYCN,-luc)Jhsc/Gt(ROSA)26Sor+
Ptentm2.1Ppp/Ptentm2.1Ppp
Rb1tm2Brn/Rb1tm2Brn
Tg(Pbsn-cre)4Prb/0
involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2 MGI:7277819
cn21
Gt(ROSA)26Sortm1(CAG-MYCN,-luc)Jhsc/Gt(ROSA)26Sor+
Ptentm2.1Ppp/Ptentm2.1Ppp
Rb1tm2Brn/Rb1+
Tg(Pbsn-cre)4Prb/0
involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2 MGI:7277820
cn22
Ptentm2.1Ppp/Ptentm2.1Ppp
Rb1tm2Brn/Rb1tm2Brn
Tg(Pbsn-cre)4Prb/0
involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2 MGI:7277828
cn23
Rb1tm2Brn/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1tm1Tyj
Rbl2tm2Tyj/Rbl2tm2Tyj
involves: 129 * 129S2/SvPas * 129S4/SvJae MGI:5789748
cn24
Rb1tm2Brn/Rb1tm2Brn
Rbl2tm1Tyj/Rbl2tm1Tyj
Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds
involves: 129 * 129S2/SvPas * FVB/N MGI:3710679
cn25
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sortm1Sor
Ptentm1Mro/Ptentm1Mro
Rb1tm2Brn/Rb1tm2Brn
involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB MGI:5563246
cn26
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brd/Trp53+
Tg(Rbp3-cre)1Brn/0
involves: 129 * 129S7/SvEvBrd * C57BL/6 * FVB/N MGI:2653661
cn27
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brd/Trp53tm1Brd
Tg(Gfap-cre)2Brn/0
involves: 129 * 129S7/SvEvBrd * FVB/N MGI:3804216
cn28
Rb1tm2Brn/Rb1tm2Brn
Tg(Pou4f3-cre)1Devet/0
involves: 129 * 129S/SvEv MGI:3639920
cn29
Rb1tm2Brn/Rb1tm2Brn
Tg(Cyp1a1-cre)1Dwi/0
involves: 129 * C57BL/6 * CBA MGI:5614112
cn30
Ccnd3tm1Pisc/Ccnd3tm1Pisc
Rb1tm2Brn/Rb1tm2Brn
Tg(Mx1-cre)1Cgn/0
involves: 129 * C57BL/6 * CBA MGI:5468652
cn31
Rb1tm2Brn/Rb1tm2Brn
Tg(KRT14-cre)8Brn/0
Tg(KRT5-Akt1*)Jmpa/0
involves: 129 * C57BL/6 * DBA/2 * DBA/2J * FVB/N MGI:3842836
cn32
Rb1tm2Brn/Rb1tm2Brn
Tg(Col1a1-cre)1Bek/0
involves: 129 * CD-1 MGI:3574808
cn33
Rb1tm2Brn/Rb1tm2Brn
Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds
involves: 129 * FVB MGI:3710677
cn34
Rb1tm2Brn/Rb1tm2Brn
Tg(Rbp3-cre)1Brn/0
involves: 129 * FVB/N MGI:2653660
cn35
Rb1tm2Brn/Rb1tm2Brn
Tg(Gfap-cre)2Brn/0
involves: 129 * FVB/N MGI:3804218
cn36
Nell1tm1Kuv/Nell1tm1Kuv
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(BGLAP-cre)1Clem/0
involves: 129 * FVB/NJ MGI:7482567
cn37
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
involves: 129P2/OlaHsd MGI:4437461
cn38
Rb1tm2Brn/Rb1+
Trp53tm1Brn/Trp53tm1Brn
involves: 129P2/OlaHsd MGI:5704166
cn39
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53+
involves: 129P2/OlaHsd MGI:4437462
cn40
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1tm1Tyj
Trp53tm1Brn/Trp53tm1Brn
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL MGI:3710238
cn41
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1tm1Tyj
Trp53tm1Brn/Trp53tm1Tyj
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL MGI:3710239
cn42
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1+
Trp53tm1Brn/Trp53tm1Brn
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL MGI:3710240
cn43
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1+
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL MGI:3710241
cn44
Rb1tm2Brn/Rb1tm2Brn
Rbl1tm1Htr/Rbl1+
Trp53tm1Brn/Trp53tm1Brn
Tg(En2-cre)22Alj/0
involves: 129P2/OlaHsd * CD-1 MGI:3707502
cn45
Rb1tm2Brn/Rb1tm2Brn
Rbl1tm1Htr/Rbl1+
Tg(En2-cre)22Alj/0
involves: 129P2/OlaHsd * CD-1 MGI:3707499
cn46
Rb1tm2Brn/Rb1tm2Brn
Rbl1tm1Htr/Rbl1tm1Htr
Tg(En2-cre)22Alj/0
involves: 129P2/OlaHsd * CD-1 MGI:3707498
cn47
Rb1tm2Brn/Rb1tm2Brn
Tg(En2-cre)22Alj/0
involves: 129P2/OlaHsd * CD-1 MGI:3707497
cn48
Rb1tm2Brn/Rb1tm2Brn
Tg(Pcp2-cre)756Mro/0
involves: 129P2/OlaHsd * FVB MGI:3707501
cn49
Rb1tm2Brn/Rb1tm2Brn
Rbl1tm1Htr/Rbl1tm1Htr
Tg(Pcp2-cre)756Mro/0
involves: 129P2/OlaHsd * FVB MGI:3707500
cn50
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Gfap-cre)2Brn/0
involves: 129P2/OlaHsd * FVB/N MGI:3804217
cn51
Ccnd3tm1Pisc/Ccnd3tm1Pisc
Cdkn1btm1Mlf/Cdkn1btm1Mlf
Rb1tm2Brn/Rb1tm2Brn
Tg(Mx1-cre)1Cgn/0
involves: 129S4/SvJaeSor * C57BL/6 * CBA MGI:5468653
cn52
Rb1tm1Dwg/Rb1tm2Brn
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
involves: 129/Sv * C57BL/6 * SJL MGI:3618365


Genotype
MGI:4437463
cn1
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Genetic
Background
involves: 129
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
N
• mice treated with a cre-expressing adenovirus exhibit normal lungs with no lesions (J:86077)
• following treatment with cre-expressing adenovirus, mice do not develop lung tumors (J:157319)

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




Genotype
MGI:4353993
cn2
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Genetic
Background
involves: 129 * BALB/c
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
adipose tissue
• following transfection with adeno-cre, preadipocyte differentiation is almost completely blocked unlike in wild-type cells




Genotype
MGI:5437517
cn3
Allelic
Composition
Gt(ROSA)26Sortm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor+
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Gfap-cre)2Brn/0
Genetic
Background
either: (involves: 129 * 129P2/OlaHsd * FVB/N) or (involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB/N)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(CAG-Bmi1,-EGFP)Nki mutation (0 available); any Gt(ROSA)26Sor mutation (968 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Gfap-cre)2Brn mutation (1 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• as in Rb1tm2Brn/Rb1tm2Brn Trp53tm1Brn/Trp53tm1Brn Tg(Gfap-cre)2Brn mice
• large cell carcinoma

endocrine/exocrine glands

nervous system
• as in Rb1tm2Brn/Rb1tm2Brn Trp53tm1Brn/Trp53tm1Brn Tg(Gfap-cre)2Brn mice




Genotype
MGI:5437516
cn4
Allelic
Composition
Gt(ROSA)26Sortm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor+
Rb1tm2Brn/Rb1tm2Brn
Tg(Gfap-cre)2Brn/0
Genetic
Background
either: (involves: 129 * 129P2/OlaHsd * FVB/N) or (involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB/N)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(CAG-Bmi1,-EGFP)Nki mutation (0 available); any Gt(ROSA)26Sor mutation (968 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Gfap-cre)2Brn mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

neoplasm
N
• mice do not develop medulloblastoma

endocrine/exocrine glands

nervous system




Genotype
MGI:4837143
cn5
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Tg(MMTV-cre)105Ayn/0
Genetic
Background
FVB.Cg-Rb1tm2Brn Tg(MMTV-cre)105Ayn
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(MMTV-cre)105Ayn mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
N
• mice do not develop mammary neoplasms




Genotype
MGI:4837145
cn6
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(MMTV-cre)105Ayn/0
Genetic
Background
FVB.Cg-Trp53tm1Brn Rb1tm2Brn Tg(MMTV-cre)105Ayn
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(MMTV-cre)105Ayn mutation (0 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• 15 of 17 mice develop mammary neoplasms
• mammary tumor cells exhibit increased genomic instability compared to in Trp53tm1Brn/Trp53tm1Brn Tg(MMTV-cre)105Ayn mice
• cell proliferation in mammary carcinomas is increased compared to in Trp53tm1Brn/Trp53tm1Brn Tg(MMTV-cre)105Ayn mice
• 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
• 1 adenosquamous carcinoma
• 4 of 40 mice develop lung metastasis

cellular
• mammary tumor cells exhibit increased genomic instability compared to in Trp53tm1Brn/Trp53tm1Brn Tg(MMTV-cre)105Ayn mice

endocrine/exocrine glands
• 15 of 17 mice develop mammary neoplasms
• mammary tumor cells exhibit increased genomic instability compared to in Trp53tm1Brn/Trp53tm1Brn Tg(MMTV-cre)105Ayn mice

integument
• 15 of 17 mice develop mammary neoplasms
• mammary tumor cells exhibit increased genomic instability compared to in Trp53tm1Brn/Trp53tm1Brn Tg(MMTV-cre)105Ayn mice

respiratory system
• 4 of 40 mice develop lung metastasis




Genotype
MGI:5441551
cn7
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Lejo/Trp53tm1Lejo
Genetic
Background
involves: 129
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Trp53tm1Lejo mutation (0 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
• 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
• 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
• neuroendocrine hyperplasia is detected at 8 weeks post infection with Ad-FIC

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
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Ren-cre)#Kwg/0
Genetic
Background
involves: 129 * 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Ren-cre)#Kwg mutation (0 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• pancreatic tumors and liver metastasis express high levels of glucagon and mice exhibit increased circulating glucagon levels indicating that tumors are glucagonoma
• 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
• metastasis to the liver and lymph node is seen; liver metastases are nodular and highly vascularized
• liver also contains many separate metastatic foci
• 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
• pancreatic tumors and liver metastasis express high levels of glucagon and mice exhibit increased circulating glucagon levels indicating that tumors are glucagonoma
• 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
• 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
• mice show increased circulating glucagon levels at 4, 5 and 6 months but not at 2 months of age

growth/size/body
• 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
Prkar1atm1.2Lsk/Prkar1a+
Rb1tm2Brn/Rb1+
Tg(Col1a1-cre)1Kry/0
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129 * 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prkar1atm1.2Lsk mutation (1 available); any Prkar1a mutation (19 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Col1a1-cre)1Kry mutation (2 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice survive to around 13.9 weeks
• treatment of mice with RANK-Fc prolongs survival to around 17.8 weeks

neoplasm
• 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
• 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
• in a scratch wound healing assay, tumor cells show greater migration than tumor cells from conditional Rb1tm2Brn heterozygous Trp53tm1Brn 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
Prkar1atm1.2Lsk/Prkar1a+
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Col1a1-cre)1Kry/0
Genetic
Background
involves: 129 * 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prkar1atm1.2Lsk mutation (1 available); any Prkar1a mutation (19 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Col1a1-cre)1Kry mutation (2 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice do not live longer than 11 weeks
• treatment of mice with RANK-Fc prolongs survival to around to around 13.3 weeks

neoplasm
• 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
• 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
Calcatm1.1(cre/ERT2)Ptch/Calca+
Trp53tm1Brn/Trp53tm1Brn
Rb1tm2Brn/Rb1tm2Brn
Ptentm1Hwu/Ptentm1Hwu
Genetic
Background
involves: 129 * 129P2/OlaHsd * 129S4/SvJae * BALB/c * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Calcatm1.1(cre/ERT2)Ptch mutation (0 available); any Calca mutation (21 available)
Ptentm1Hwu mutation (16 available); any Pten mutation (83 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• death within 3 months of tamoxifen treatment

respiratory system
• small cell lung tumors 2.5 months after tamoxifen treatment
• increased proliferation of pulmonary neuroendocrine cells

neoplasm
• all mice develop thyroid tumors
• increased invasiveness at 2.5 months after tamoxifen treatment
• small cell lung tumors 2.5 months after tamoxifen treatment

endocrine/exocrine glands
• all mice develop thyroid tumors




Genotype
MGI:5563247
cn12
Allelic
Composition
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sortm1Sor
Ptentm1Mro/Ptentm1Mro
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129 * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1Sor mutation (7 available); any Gt(ROSA)26Sor mutation (968 available)
Ptentm1Mro mutation (1 available); any Pten mutation (83 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• 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
• 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)26Sortm1Sor/Gt(ROSA)26Sortm1Sor
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129 * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1Sor mutation (7 available); any Gt(ROSA)26Sor mutation (968 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• 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
• 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
Dlg2tm1a(EUCOMM)Wtsi/Dlg2tm1a(EUCOMM)Wtsi
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Col1a1-cre)1Kry/0
Genetic
Background
involves: 129 * 129P2/OlaHsd * C57BL/6N * FVB/N
Cell Lines EPD0635_5_E12
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dlg2tm1a(EUCOMM)Wtsi mutation (1 available); any Dlg2 mutation (62 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Col1a1-cre)1Kry mutation (2 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
• tumor cells are more proliferative than those in control littermates that are wild-type for Dlg2, as indicated by Ki-67 staining
• 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
• 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
• 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:5796164
cn15
Allelic
Composition
Rb1tm2Brn/Rb1+
Trp53tm1Brn/Trp53tm1Brn
Tg(Col1a1-cre)1Kry/0
Genetic
Background
involves: 129 * 129P2/OlaHsd * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Col1a1-cre)1Kry mutation (2 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice survive up to 55.4 weeks of age

neoplasm
• mice develop osteosarcoma by 35 weeks of age
• tumors are marked by low TNFSF11 (RANKL)/high TNFRSF11A (RANK) levels

skeleton
• mice develop osteosarcoma by 35 weeks of age
• tumors are marked by low TNFSF11 (RANKL)/high TNFRSF11A (RANK) levels




Genotype
MGI:5437518
cn16
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Gfap-cre)2Brn/0
Genetic
Background
involves: 129 * 129P2/OlaHsd * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Gfap-cre)2Brn mutation (1 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype



Genotype
MGI:5796161
cn17
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Col1a1-cre)1Kry/0
Genetic
Background
involves: 129 * 129P2/OlaHsd * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Col1a1-cre)1Kry mutation (2 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice survive up to 38.1 weeks of age

neoplasm
• mice develop osteosarcoma by 20 weeks of age

skeleton
• mice develop osteosarcoma by 20 weeks of age




Genotype
MGI:5460840
cn18
Allelic
Composition
Calcatm1.1(cre/ERT2)Ptch/Calca+
Trp53tm1Brn/Trp53tm1Brn
Rb1tm2Brn/Rb1tm2Brn
Genetic
Background
involves: 129 * 129P2/OlaHsd * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Calcatm1.1(cre/ERT2)Ptch mutation (0 available); any Calca mutation (21 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• death within 6-7 months of tamoxifen treatment

respiratory system
• small cell lung tumors 5-6 months after tamoxifen treatment in 4 of 32 mice examined, all with pulmonary neuroendocrine cells hyperplasia as well
• pulmonary neuroendocrine cells hyperplasia 5-6 months after tamoxifen treatment in 16 of 32 mice examined
• increased proliferation of pulmonary neuroendocrine cells

neoplasm
• all mice develop thyroid tumors
• 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
• all mice develop thyroid tumors




Genotype
MGI:7482566
cn19
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(BGLAP-cre)1Clem/0
Genetic
Background
involves: 129 * 129P2/OlaHsd * FVB/NJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(BGLAP-cre)1Clem mutation (1 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• tumor-free survival is 146.5 days

neoplasm

skeleton




Genotype
MGI:7277819
cn20
Allelic
Composition
Gt(ROSA)26Sortm1(CAG-MYCN,-luc)Jhsc/Gt(ROSA)26Sor+
Ptentm2.1Ppp/Ptentm2.1Ppp
Rb1tm2Brn/Rb1tm2Brn
Tg(Pbsn-cre)4Prb/0
Genetic
Background
involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(CAG-MYCN,-luc)Jhsc mutation (0 available); any Gt(ROSA)26Sor mutation (968 available)
Ptentm2.1Ppp mutation (0 available); any Pten mutation (83 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Pbsn-cre)4Prb mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• median survival time of 12.5 weeks
• castrated mice have a median survival time of 24 weeks

neoplasm
• 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
• 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
• 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
• 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

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)26Sortm1(CAG-MYCN,-luc)Jhsc/Gt(ROSA)26Sor+
Ptentm2.1Ppp/Ptentm2.1Ppp
Rb1tm2Brn/Rb1+
Tg(Pbsn-cre)4Prb/0
Genetic
Background
involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(CAG-MYCN,-luc)Jhsc mutation (0 available); any Gt(ROSA)26Sor mutation (968 available)
Ptentm2.1Ppp mutation (0 available); any Pten mutation (83 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Pbsn-cre)4Prb mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• median survival time of 19 weeks

neoplasm
• 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
• 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
• 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
Ptentm2.1Ppp/Ptentm2.1Ppp
Rb1tm2Brn/Rb1tm2Brn
Tg(Pbsn-cre)4Prb/0
Genetic
Background
involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm2.1Ppp mutation (0 available); any Pten mutation (83 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Pbsn-cre)4Prb mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• median survival time of 38 weeks
• castrated mice have a median survival time of 43.5 weeks

neoplasm
• 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
• 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
• 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
Rb1tm2Brn/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1tm1Tyj
Rbl2tm2Tyj/Rbl2tm2Tyj
Genetic
Background
involves: 129 * 129S2/SvPas * 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (60 available)
Rbl2tm2Tyj mutation (2 available); any Rbl2 mutation (52 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• 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 is sometimes seen in mice injected with AdCre into the bladder lumen with bladder lesions
• 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 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
Rb1tm2Brn/Rb1tm2Brn
Rbl2tm1Tyj/Rbl2tm1Tyj
Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds
Genetic
Background
involves: 129 * 129S2/SvPas * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Rbl2tm1Tyj mutation (1 available); any Rbl2 mutation (52 available)
Tg(Myh6-cre)2182Mds mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 36% die suddenly by 12 weeks of age and only 48% survive to 6 months of age

cardiovascular system
• cardiomyocytes have an increase in diameter and contain large, hyperchromatic nuclei
• 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
• mutants surviving to 12 weeks of age show evidence of LV dilation
• 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
• seen in mutants surviving to 12 weeks of age
• hearts exhibit persistent myocyte cycling

respiratory system
• 36% develop signs of respiratory distress

homeostasis/metabolism
• 36% develop signs of generalized edema

muscle
• cardiomyocytes have an increase in diameter and contain large, hyperchromatic nuclei
• 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
• 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)26Sortm1Sor/Gt(ROSA)26Sortm1Sor
Ptentm1Mro/Ptentm1Mro
Rb1tm2Brn/Rb1tm2Brn
Genetic
Background
involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1Sor mutation (7 available); any Gt(ROSA)26Sor mutation (968 available)
Ptentm1Mro mutation (1 available); any Pten mutation (83 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
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
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brd/Trp53+
Tg(Rbp3-cre)1Brn/0
Genetic
Background
involves: 129 * 129S7/SvEvBrd * C57BL/6 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Rbp3-cre)1Brn mutation (0 available)
Trp53tm1Brd mutation (5 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• loss of heterozygosity of Trp53 in the neuroendocrine tumors
• develop pituitary gland and pineal gland tumors
• pinealoblastomas locally invade the brain




Genotype
MGI:3804216
cn27
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brd/Trp53tm1Brd
Tg(Gfap-cre)2Brn/0
Genetic
Background
involves: 129 * 129S7/SvEvBrd * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Gfap-cre)2Brn mutation (1 available)
Trp53tm1Brd mutation (5 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• 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
• loss of balance
• mutants hold their heads to one side
• gait is disturbed with ataxia

nervous system
• 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
Rb1tm2Brn/Rb1tm2Brn
Tg(Pou4f3-cre)1Devet/0
Genetic
Background
involves: 129 * 129S/SvEv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Pou4f3-cre)1Devet mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• at 3 and 6 months, mutants are unable to swim with their heads above water
• at 3 and 6 months, mutants display moderate circling behavior

hearing/vestibular/ear
• at P17, cochlear supporting cells are proliferating but in wild-type no proliferation is occurring at this age
• in the basal turn, the tunnel of corti has collapsed in 6-week old animals
• at P1 cochlear hair cells are still undergoing proliferation but in wild-type no proliferation is occurring at this age
• more inner hair cells than wild-type
• many outer hair cells lack bundles; atypical bundles including ring-shaped bundles and 2 bundles within one hair cell are occasionally observed
• more outer hair cells than wild-type
• total hair cell loss by 3 months of age
• from P6 to P17, there is apoptosis in the outer hair cell region of the organ of corti
• at P17, utrical hair cells are proliferating but in wild-type no proliferation is occurring at this age
• 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
• mice are profoundly deaf by 3 months of age when all hair cells are lost
• 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
• at P1 cochlear hair cells are still undergoing proliferation but in wild-type no proliferation is occurring at this age
• more inner hair cells than wild-type
• many outer hair cells lack bundles; atypical bundles including ring-shaped bundles and 2 bundles within one hair cell are occasionally observed
• more outer hair cells than wild-type
• total hair cell loss by 3 months of age
• from P6 to P17, there is apoptosis in the outer hair cell region of the organ of corti
• at P17, utrical hair cells are proliferating but in wild-type no proliferation is occurring at this age
• 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
• at P17, cochlear supporting cells are proliferating but in wild-type no proliferation is occurring at this age




Genotype
MGI:5614112
cn29
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Tg(Cyp1a1-cre)1Dwi/0
Genetic
Background
involves: 129 * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Cyp1a1-cre)1Dwi mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• increased proliferation of columnar epithelial cells of the villi

digestive/alimentary system
• increased proliferation of columnar epithelial cells of the villi




Genotype
MGI:5468652
cn30
Allelic
Composition
Ccnd3tm1Pisc/Ccnd3tm1Pisc
Rb1tm2Brn/Rb1tm2Brn
Tg(Mx1-cre)1Cgn/0
Genetic
Background
involves: 129 * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccnd3tm1Pisc mutation (0 available); any Ccnd3 mutation (507 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Mx1-cre)1Cgn mutation (7 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• of pre-T cells as in Ccnd3tm1Pisc homozygotes
• not as severe as in pIpC-treated mice as in Ccnd3tm1Pisc homozygotes
• as in Ccnd3tm1Pisc homozygotes

hematopoietic system
• of pre-T cells as in Ccnd3tm1Pisc homozygotes
• not as severe as in pIpC-treated mice as in Ccnd3tm1Pisc homozygotes
• as in Ccnd3tm1Pisc homozygotes

endocrine/exocrine glands
• not as severe as in pIpC-treated mice as in Ccnd3tm1Pisc homozygotes

cellular
• of pre-T cells as in Ccnd3tm1Pisc homozygotes




Genotype
MGI:3842836
cn31
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Tg(KRT14-cre)8Brn/0
Tg(KRT5-Akt1*)Jmpa/0
Genetic
Background
involves: 129 * C57BL/6 * DBA/2 * DBA/2J * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(KRT14-cre)8Brn mutation (4 available)
Tg(KRT5-Akt1*)Jmpa mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• pathologic characteristics of oral lesions and tumor development rate are the same as in Tg(KRT5-Akt1*)Jmpa mice

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

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

growth/size/body
• 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
Rb1tm2Brn/Rb1tm2Brn
Tg(Col1a1-cre)1Bek/0
Genetic
Background
involves: 129 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Col1a1-cre)1Bek mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

hearing/vestibular/ear
• 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
• proliferating cells were found in the zone of nonproliferating cells in the primordial organ of Corti at E13.5
• 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
• cochleas had 3-4 rows of inner hair cells compared to one row of inner hair cells in wildtype
• cochleas had 7-8 rows of outer hair cells compared to 3 rows of outer hair cells in wildtype
• 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
• 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
• transduction currents in ear hair cells were smaller than in controls (10-20 pA versus 200 pA in controls)

nervous system
• 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
• cochleas had 3-4 rows of inner hair cells compared to one row of inner hair cells in wildtype
• cochleas had 7-8 rows of outer hair cells compared to 3 rows of outer hair cells in wildtype
• 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
• 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
Rb1tm2Brn/Rb1tm2Brn
Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds
Genetic
Background
involves: 129 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Myh6-cre)2182Mds mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• 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:2653660
cn34
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Tg(Rbp3-cre)1Brn/0
Genetic
Background
involves: 129 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Rbp3-cre)1Brn mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• develop pituitary gland tumors that arise from the anterior lobe of the pituitary gland
• however, do not develop retinoblastomas or pineal gland tumors
• develop pituitary gland tumors that arise from the intermediate lobe of the pituitary gland

endocrine/exocrine glands
• develop pituitary gland tumors that arise from the anterior lobe of the pituitary gland
• however, do not develop retinoblastomas or pineal gland tumors
• develop pituitary gland tumors that arise from the intermediate lobe of the pituitary gland

vision/eye
N
• retinas appear normal

nervous system
• develop pituitary gland tumors that arise from the anterior lobe of the pituitary gland
• however, do not develop retinoblastomas or pineal gland tumors
• develop pituitary gland tumors that arise from the intermediate lobe of the pituitary gland




Genotype
MGI:3804218
cn35
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Tg(Gfap-cre)2Brn/0
Genetic
Background
involves: 129 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Gfap-cre)2Brn mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

neoplasm
N
• mutants do not develop medulloblastomas
• large cell carcinoma

endocrine/exocrine glands

nervous system




Genotype
MGI:7482567
cn36
Allelic
Composition
Nell1tm1Kuv/Nell1tm1Kuv
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(BGLAP-cre)1Clem/0
Genetic
Background
involves: 129 * FVB/NJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nell1tm1Kuv mutation (1 available); any Nell1 mutation (57 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(BGLAP-cre)1Clem mutation (1 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• tumor-free survival is 398 days compared to 146.5 days in mutant mice wild-type for Nell1

neoplasm
• 85.2% decrease in the proliferative-index in tumors compared to tumors in mutant mice wild-type for Nell1
• 66.1% decrease in tumor-associated vasculature compared to mutant mice wild-type for Nell1
• 15.8% incidence compared to 52.4% incidence in mutant mice wild-type for Nell1

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




Genotype
MGI:4437461
cn37
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• 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
• the ovarian cancer found after a single ovarian intrabursal injection of an adenovirus expressing Cre is characterisitic of serous adenocarcinoma
• 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)

mortality/aging
• 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
• 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
• the ovarian cancer found after a single ovarian intrabursal injection of an adenovirus expressing Cre is characterisitic of serous adenocarcinoma
• 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)
• various metastases in some mice treated with a cre-expressing adenovirus
• 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
• mice treated with cre-expressing adenovirus median tumor-free survival is 210 days
• bronchioalveolar carcinomas in some mice treated with a cre-expressing adenovirus
• 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
• 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
• the ovarian cancer found after a single ovarian intrabursal injection of an adenovirus expressing Cre is characterisitic of serous adenocarcinoma

respiratory system
• mice treated with cre-expressing adenovirus median tumor-free survival is 210 days
• bronchioalveolar carcinomas in some mice treated with a cre-expressing adenovirus
• 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)




Genotype
MGI:5704166
cn38
Allelic
Composition
Rb1tm2Brn/Rb1+
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• some mice treated with a cre-expressing adenovirus exhibit metastasis in the mediastinum, ovary and adrenal gland
• in some mice treated with a cre-expressing adenovirus
• small in some mice treated with a cre-expressing adenovirus

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




Genotype
MGI:4437462
cn39
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53+
Genetic
Background
involves: 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• 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)
• mice treated with cre-expressing adenovirus median tumor-free survival is 475 days
• in some mice treated with a cre-expressing adenovirus (J:86077)
• in some mice following treatment with cre-expressing adenovirus (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
• 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
• mice treated with cre-expressing adenovirus median tumor-free survival is 475 days
• in some mice treated with a cre-expressing adenovirus (J:86077)
• in some mice following treatment with cre-expressing adenovirus (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:3710238
cn40
Allelic
Composition
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1tm1Tyj
Trp53tm1Brn/Trp53tm1Brn
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
Genetic
Background
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (60 available)
Tg(Chx10-EGFP/cre,-ALPP)2Clc mutation (1 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• 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
• 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
• 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
• 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

neoplasm
• 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:3710239
cn41
Allelic
Composition
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1tm1Tyj
Trp53tm1Brn/Trp53tm1Tyj
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
Genetic
Background
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (60 available)
Tg(Chx10-EGFP/cre,-ALPP)2Clc mutation (1 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
Trp53tm1Tyj mutation (12 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• 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
• 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
• 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
• 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
• a substantial proportion of tumor cells expressing amacrine/horizontal cell markers are proliferating as shown by labeled thymidine incorporation




Genotype
MGI:3710240
cn42
Allelic
Composition
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1+
Trp53tm1Brn/Trp53tm1Brn
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
Genetic
Background
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (60 available)
Tg(Chx10-EGFP/cre,-ALPP)2Clc mutation (1 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• significant disruptions in retinal morphology are observed by P12 to 13
• 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

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




Genotype
MGI:3710241
cn43
Allelic
Composition
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1+
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
Genetic
Background
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (60 available)
Tg(Chx10-EGFP/cre,-ALPP)2Clc mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• mice with retinoblastoma tumors are characterized by pronounced loss of photoreceptor cells

neoplasm
• 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
• 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
• 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
• significant disruptions in retinal morphology are observed by P12 to 13
• mice with retinoblastoma tumors are characterized by pronounced loss of photoreceptor cells




Genotype
MGI:3707502
cn44
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Rbl1tm1Htr/Rbl1+
Trp53tm1Brn/Trp53tm1Brn
Tg(En2-cre)22Alj/0
Genetic
Background
involves: 129P2/OlaHsd * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Rbl1tm1Htr mutation (0 available); any Rbl1 mutation (60 available)
Tg(En2-cre)22Alj mutation (1 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
N
• mice have similar levels of apoptosis in the cerebella as Rb1, Rbl1 double mutants which express Trp53




Genotype
MGI:3707499
cn45
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Rbl1tm1Htr/Rbl1+
Tg(En2-cre)22Alj/0
Genetic
Background
involves: 129P2/OlaHsd * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Rbl1tm1Htr mutation (0 available); any Rbl1 mutation (60 available)
Tg(En2-cre)22Alj mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• mutants develop ataxia between P15 and P20

nervous system
• 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
• at P15, number of proliferating granule cell precursors in external granule layer is higher than in controls
• at P15, the vermis is considerably reduced in size, but less than when both Rbl1 alleles are lost
• at P15, size reduction compared to wild-type cerebella is noticed

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




Genotype
MGI:3707498
cn46
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Rbl1tm1Htr/Rbl1tm1Htr
Tg(En2-cre)22Alj/0
Genetic
Background
involves: 129P2/OlaHsd * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Rbl1tm1Htr mutation (0 available); any Rbl1 mutation (60 available)
Tg(En2-cre)22Alj mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• mutants develop ataxia between P15 and P20

nervous system
• increased proliferation is even more pronounced in cerebella of mutants at P15 and 20
• at P20, mice have highly disorganized cerebellar architecture in median cerebellar region
• 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
• layer is reduce in size
• at P15, the vermis is severely reduced in size

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




Genotype
MGI:3707497
cn47
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Tg(En2-cre)22Alj/0
Genetic
Background
involves: 129P2/OlaHsd * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(En2-cre)22Alj mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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
• 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
• 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)
• at P20, mice have a persisten thin EGL with granule cell precursors still migrating through the molecular layer
• interneurons of molecular layer of cerebellum are substantially reduced in number at P20, which is most pronounced in lobules VI and VII
• numbers of granule, basket and stellate neurons are considerably reduced compared to wild-type
• 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
• 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
• numbers are severely reduced in cerebellum
• a brisk widespread astrogliosis in observed in the IGL

cellular
• 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
• 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:3707501
cn48
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Tg(Pcp2-cre)756Mro/0
Genetic
Background
involves: 129P2/OlaHsd * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Pcp2-cre)756Mro mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• at P15, the vermis is considerably reduced in size, but less than when both Rbl1 alleles are lost




Genotype
MGI:3707500
cn49
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Rbl1tm1Htr/Rbl1tm1Htr
Tg(Pcp2-cre)756Mro/0
Genetic
Background
involves: 129P2/OlaHsd * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Rbl1tm1Htr mutation (0 available); any Rbl1 mutation (60 available)
Tg(Pcp2-cre)756Mro mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• some Purkinje cells show enlarged nuclei with abnormal hourglass or kidney shapes




Genotype
MGI:3804217
cn50
Allelic
Composition
Rb1tm2Brn/Rb1tm2Brn
Trp53tm1Brn/Trp53tm1Brn
Tg(Gfap-cre)2Brn/0
Genetic
Background
involves: 129P2/OlaHsd * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Gfap-cre)2Brn mutation (1 available)
Trp53tm1Brn mutation (18 available); any Trp53 mutation (232 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• mutants develop medulloblastomas

nervous system
• 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
Ccnd3tm1Pisc/Ccnd3tm1Pisc
Cdkn1btm1Mlf/Cdkn1btm1Mlf
Rb1tm2Brn/Rb1tm2Brn
Tg(Mx1-cre)1Cgn/0
Genetic
Background
involves: 129S4/SvJaeSor * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccnd3tm1Pisc mutation (0 available); any Ccnd3 mutation (507 available)
Cdkn1btm1Mlf mutation (2 available); any Cdkn1b mutation (26 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Mx1-cre)1Cgn mutation (7 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
N
• mice exhibit normal numbers of thymocytes, double negative cells, double positive cells and pre-T cell proliferation




Genotype
MGI:3618365
cn52
Allelic
Composition
Rb1tm1Dwg/Rb1tm2Brn
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
Genetic
Background
involves: 129/Sv * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Dwg mutation (0 available); any Rb1 mutation (107 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Chx10-EGFP/cre,-ALPP)2Clc mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• significant reduction in rod photoreceptors at P14, however no changes in the number of other major cell types in the retina
• horizontal cell synaptogenesis in the retina is defective

nervous system
• significant reduction in rod photoreceptors at P14, however no changes in the number of other major cell types in the retina
• horizontal cell synaptogenesis in the retina is defective





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last database update
07/05/2024
MGI 6.24
The Jackson Laboratory