All Phenotypes Rb1<+> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Rb1⁺
wild type
MGI:1857403

Summary

41 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Rb1^tm1Mlh/Rb1⁺	either: 129P2/OlaHsd-Rb1^tm1Mlh or (involves: 129P2/OlaHsd * BALB/c) or (involves: 129P2/OlaHsd * FVB/N)	MGI:3574050
ht2	Rb1^tm2Mlh/Rb1⁺	either: 129P2/OlaHsd-Rb1^tm2Mlh or (involves: 129P2/OlaHsd * BALB/c) or (involves: 129P2/OlaHsd * FVB/N)	MGI:3574052
ht3	Rb1^tm1.1Jyjw/Rb1⁺	either: (involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6) or (involves: 129S4/SvJae * 129S6/SvEvTac)	MGI:3769471
ht4	Rb1^tm1Jyjw/Rb1⁺	either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * C57BL/6)	MGI:3769470
ht5	Rb1^tm1Brd/Rb1⁺	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J	MGI:3834166
ht6	Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas	MGI:5614091
ht7	Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296667
ht8	Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * C57BL/6	MGI:3582548
ht9	Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * C57BL/6J	MGI:3839771
ht10	Rb1^tm1Brd/Rb1⁺	involves: 129S7/SvEvBrd * C57BL/6	MGI:2684728
ht11	Rb1^tm1.2Gfk/Rb1⁺	involves: 129T2/SvEms * C57BL/6 * SJL	MGI:3624446
cn12	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
cn13	Rb1^tm2Brn/Rb1⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Col1a1-cre)1Kry/0	involves: 129 * 129P2/OlaHsd * FVB/N	MGI:5796164
cn14	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
cn15	Rb1^tm3Tyj/Rb1⁺ Sox2^tm4.1Skn/Sox2^tm4.1Skn Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129 * C57BL/6 * CD-1	MGI:7484195
cn16	Rb1^tm3Tyj/Rb1⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129 * C57BL/6 * CD-1	MGI:7484192
cn17	Rb1^tm3Tyj/Rb1⁺ Sox2^tm4.1Skn/Sox2⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129 * C57BL/6 * CD-1	MGI:7484197
cn18	Rb1^tm2Brn/Rb1⁺ Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd	MGI:5704166
cn19	Rb1^tm3Tyj/Rb1⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N	MGI:5519095
cn20	Rb1^tm3Tyj/Rb1⁺ Trp53^tm1Brn/Trp53⁺ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N	MGI:5519097
cn21	Rb1^tm1Brn/Rb1⁺ X/Tg(Pomc-FLP)1bBrn	involves: 129P2/OlaHsd * FVB/N	MGI:4353105
cn22	Rb1^tm1Brn/Rb1⁺ Tg(Pomc-FLP)1aBrn/0	involves: 129P2/OlaHsd * FVB/N	MGI:4353103
cx23	E2f1^tm1Njd/E2f1^tm1Njd Rb1^tm1Tyj/Rb1⁺	either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)	MGI:3840353
cx24	E2f1^tm1Njd/E2f1⁺ Rb1^tm1Tyj/Rb1⁺	either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)	MGI:3840352
cx25	Rb1^tm1Fad/Rb1⁺ Tg(KRT14-HPV16E7)2304Plam/0	involves: 129 * C57BL/6 * FVB	MGI:3607131
cx26	Msh2^tm1Whl/Msh2^tm1Whl Rb1^tm1Brd/Rb1⁺	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J	MGI:3834164
cx27	Rb1^tm1Tyj/Rb1⁺ Trim27^{Gt(XP0484)Wtsi}/Trim27^{Gt(XP0484)Wtsi}	involves: 129P2/OlaHsd * C57BL/6	MGI:5446920
cx28	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Rb1^tm1Tyj/Rb1⁺ Tg(Rb1)1Blg/0	involves: 129S2/SvPas	MGI:4420467
cx29	Men1^tm1.1Ctre/Men1⁺ Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:3839773
cx30	Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296664
cx31	Kdm5a^tm1.1Kael/Kdm5a⁺ Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296663
cx32	Rb1^tm1Tyj/Rb1⁺ Tg(Th-MYCN)41Waw/0	involves: 129S2/SvPas * BALB/c * C57BL/6J	MGI:5009553
cx33	Rb1^tm1Tyj/Rb1⁺ Trp53^tm1Tyj/Trp53⁺	involves: 129S2/SvPas * C57BL/6	MGI:3582787
cx34	E2f4^tm1Lees/E2f4^tm1Lees Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * C57BL/6	MGI:3582517
cx35	E2f4^tm1Lees/E2f4⁺ Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * C57BL/6	MGI:3582523
cx36	Rb1^tm1Tyj/Rb1⁺ Rbl1^tm1Tyj/Rbl1^tm1Tyj	involves: 129S2/SvPas * C57BL/6	MGI:3582581
cx37	Rb1^tm1Tyj/Rb1⁺ Rbl1^tm1Tyj/Rbl1⁺	involves: 129S2/SvPas * C57BL/6	MGI:3582618
cx38	Rb1^tm1Tyj/Rb1⁺ Tg(S100b-v-erbB)4496Waw/0	involves: 129S2/SvPas * C57BL/6J * DBA/2J * FVB/N	MGI:3822322
cx39	Rb1^tm1Brd/Rb1⁺ Rr70^tm1Alb/Rr70⁺	involves: 129S7/SvEvBrd * C57BL/6	MGI:3717490
cx40	Rb1^tm1Brd/Rb1⁺ Trp53^tm1Brd/Trp53⁺	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3834167
cx41	Rb1^tm1Tyj/Rb1⁺ Smarca4^tm1Mag/Smarca4⁺	involves: 129S/Sv * 129S2/SvPas * C57BL/6J * CD-1	MGI:5763442

Allelic Composition	Rb1^tm1Mlh/Rb1⁺
Genetic Background	either: 129P2/OlaHsd-Rb1^tm1Mlh or (involves: 129P2/OlaHsd * BALB/c) or (involves: 129P2/OlaHsd * FVB/N)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Mlh mutation (0 available); any Rb1 mutation (107 available)

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

neoplasm

neoplasm ( J:2498 , J:20542 )

• up to 7 months of age, young heterozygotes exhibit no sign of retinoblastoma or any other abnormality relative to wild-type mice (J:2498)

• no retinoblastomas are macroscopically detected in chimeras ranging in age up to 11 months (J:2498)

• no pre-neoplastic lesions are detected in the medulla of the adrenal gland of heterozygous mutant mice (J:20542)

increased pituitary melanotroph tumor incidence ( J:20542 )

• after 3-5 months, heterozygotes develop large (4-5 mm) tumors in the intermediate lobe of the pituitary gland

• such tumors are relatively benign and do not infiltrate into brain tissue; the wild-type allele of Rb1 is lost in the vast majority of cases

nervous system

increased pituitary melanotroph tumor incidence ( J:20542 )

• after 3-5 months, heterozygotes develop large (4-5 mm) tumors in the intermediate lobe of the pituitary gland

• such tumors are relatively benign and do not infiltrate into brain tissue; the wild-type allele of Rb1 is lost in the vast majority of cases

abnormal dorsal root ganglion morphology ( J:2498 )

• at E11.5, heterozygotes exhibit only occasional apoptotic cells in the spinal ganglia, identified by their pyknotic and fragmented nuclei and dense eosinophilic cytoplasm

endocrine/exocrine glands

increased pituitary melanotroph tumor incidence ( J:20542 )

• after 3-5 months, heterozygotes develop large (4-5 mm) tumors in the intermediate lobe of the pituitary gland

• such tumors are relatively benign and do not infiltrate into brain tissue; the wild-type allele of Rb1 is lost in the vast majority of cases

Allelic Composition	Rb1^tm2Mlh/Rb1⁺
Genetic Background	either: 129P2/OlaHsd-Rb1^tm2Mlh or (involves: 129P2/OlaHsd * BALB/c) or (involves: 129P2/OlaHsd * FVB/N)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm2Mlh mutation (0 available); any Rb1 mutation (107 available)

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

neoplasm

neoplasm ( J:2498 , J:20542 )

• up to 7 months of age, young heterozygotes exhibit no sign of retinoblastoma or any other abnormality relative to wild-type mice (J:2498)

• no retinoblastomas are macroscopically detected in chimeras ranging in age up to 11 months (J:2498)

• no pre-neoplastic lesions are detected in the medulla of the adrenal gland of heterozygous mutant mice (J:20542)

increased pituitary melanotroph tumor incidence ( J:20542 )

• after 3-5 months, heterozygotes develop large (4-5 mm) tumors in the intermediate lobe of the pituitary gland

• such tumors are relatively benign and do not infiltrate into brain tissue; the wild-type allele of Rb1 is lost in the vast majority of cases

nervous system

increased pituitary melanotroph tumor incidence ( J:20542 )

• after 3-5 months, heterozygotes develop large (4-5 mm) tumors in the intermediate lobe of the pituitary gland

• such tumors are relatively benign and do not infiltrate into brain tissue; the wild-type allele of Rb1 is lost in the vast majority of cases

abnormal dorsal root ganglion morphology ( J:2498 )

• at E11.5, heterozygotes exhibit only occasional apoptotic cells in the spinal ganglia, identified by their pyknotic and fragmented nuclei and dense eosinophilic cytoplasm

endocrine/exocrine glands

increased pituitary melanotroph tumor incidence ( J:20542 )

• after 3-5 months, heterozygotes develop large (4-5 mm) tumors in the intermediate lobe of the pituitary gland

• such tumors are relatively benign and do not infiltrate into brain tissue; the wild-type allele of Rb1 is lost in the vast majority of cases

Allelic Composition	Rb1^tm1.1Jyjw/Rb1⁺
Genetic Background	either: (involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6) or (involves: 129S4/SvJae * 129S6/SvEvTac)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1.1Jyjw mutation (0 available); any Rb1 mutation (107 available)

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

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:80087 )

• 5 days after LPS injection, 58% of males recover compared to 33% of wild-type mice; mutant females show about 25% recovery, not significantly different from wild-type

behavior/neurological

lethargy ( J:80087 )

• sign of endotoxemia, displayed when animals are treated with LPS

abnormal pilomotor reflex ( J:80087 )

• sign of endotoxemia, displayed when animals are treated with LPS

vision/eye

decreased retina apoptosis ( J:80087 )

• in cultured retina explants, apoptosis in the ganglial cell layer (GCL) is reduced compared to wild-type explants; this protection is transient and somewhat less compared to homozygous mutants

cellular

decreased apoptosis ( J:80087 )

• in response to LPS treatment, apoptosis in the intestine is significantly reduced compared to wild-type mice

decreased retina apoptosis ( J:80087 )

• in cultured retina explants, apoptosis in the ganglial cell layer (GCL) is reduced compared to wild-type explants; this protection is transient and somewhat less compared to homozygous mutants

Allelic Composition	Rb1^tm1Jyjw/Rb1⁺
Genetic Background	either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * C57BL/6)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Jyjw mutation (0 available); any Rb1 mutation (107 available)

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

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:80087 )

• 5 days after LPS injection, 58% of males recover compared to 33% of wild-type mice; mutant females show about 25% recovery, not significantly different from wild-type

behavior/neurological

lethargy ( J:80087 )

• sign of endotoxemia, displayed when animals are treated with LPS

abnormal pilomotor reflex ( J:80087 )

• sign of endotoxemia, displayed when animals are treated with LPS

vision/eye

abnormal retina apoptosis ( J:80087 )

• in cultured retina explants, apoptosis in the ganglial cell layer (GCL) is reduced compared to wild-type explants; this protection is transient and somewhat less compared to homozygous mutants

cellular

abnormal retina apoptosis ( J:80087 )

• in cultured retina explants, apoptosis in the ganglial cell layer (GCL) is reduced compared to wild-type explants; this protection is transient and somewhat less compared to homozygous mutants

decreased apoptosis ( J:80087 )

• in response to LPS treatment, apoptosis in the intestine is significantly reduced compared to wild-type mice

Allelic Composition	Rb1^tm1Brd/Rb1⁺
Genetic Background	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Brd mutation (0 available); any Rb1 mutation (107 available)

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

neoplasm

increased pheochromocytoma incidence ( J:79016 )

• seen in most mice

increased pituitary adenohypophysis tumor incidence ( J:79016 )

• some mice develop tumors of the pituitary anterior lobe

increased pituitary melanotroph tumor incidence ( J:79016 )

• all mice develop melanotroph tumors of the pituitary

increased thyroid C-cell carcinoma incidence ( J:79016 )

• most mice develop C cell thyroid carcinomas

nervous system

increased pituitary adenohypophysis tumor incidence ( J:79016 )

• some mice develop tumors of the pituitary anterior lobe

increased pituitary melanotroph tumor incidence ( J:79016 )

• all mice develop melanotroph tumors of the pituitary

endocrine/exocrine glands

increased pheochromocytoma incidence ( J:79016 )

• seen in most mice

increased pituitary adenohypophysis tumor incidence ( J:79016 )

• some mice develop tumors of the pituitary anterior lobe

increased pituitary melanotroph tumor incidence ( J:79016 )

• all mice develop melanotroph tumors of the pituitary

increased thyroid C-cell carcinoma incidence ( J:79016 )

• most mice develop C cell thyroid carcinomas

Allelic Composition	Rb1^tm1Tyj/Rb1⁺
Genetic Background	involves: 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:215358 )

• mice develop pituitary gland tumors with a mean survival of 400 days

neoplasm

increased pituitary gland tumor incidence ( J:215358 )

• mice develop pituitary gland tumors with a mean survival of 400 days

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:215358 )

• mice develop pituitary gland tumors with a mean survival of 400 days

nervous system

increased pituitary gland tumor incidence ( J:215358 )

• mice develop pituitary gland tumors with a mean survival of 400 days

Allelic Composition	Rb1^tm1Tyj/Rb1⁺
Genetic Background	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)

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

mortality/aging

premature death ( J:175625 )

• median survival is 47 weeks

neoplasm

increased pituitary gland tumor incidence ( J:175625 )

• in 9 of 10 mice; 5 of 5 with intermediate lobe origins

increased thyroid tumor incidence ( J:175625 )

• in 8 of 10 mice

nervous system

increased pituitary gland tumor incidence ( J:175625 )

• in 9 of 10 mice; 5 of 5 with intermediate lobe origins

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:175625 )

• in 9 of 10 mice; 5 of 5 with intermediate lobe origins

increased thyroid tumor incidence ( J:175625 )

• in 8 of 10 mice

Allelic Composition	Rb1^tm1Tyj/Rb1⁺
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)

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

mortality/aging

premature death ( J:81082 )

• all heterozygous mutant mice die between 8.5 and 13.9 months of age

neoplasm

neoplasm ( J:2511 )

N	• up to 11 months of age, none of >100 heterozygotes studied show any macroscopic sign of retinoblastoma relative to wild-type mice • in addition, no precursor lesions (retinomas) are detected by indirect ophthalmology or histological evaluation

increased pituitary gland tumor incidence ( J:2511 , J:81082 )

• at autopsy, heterozygotes with severe wasting symptoms show large pituitary adenocarcinomas (~ 6 mm in diameter) (J:2511)

• consistent with the "two-hit" model proposed by Knudson, such pituitary tumors are shown to arise from cells in which the wild-type allele is absent (J:2511)

• heterozygotes develop intermediate lobe pituitary tumors (J:81082)

increased thyroid tumor incidence ( J:81082 )

• 23/27 heterozygotes show c-cell thyroid tumors

growth/size/body

cachexia ( J:2511 )

• at 8-10 months of age, a number of heterozygotes display severe wasting

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:2511 , J:81082 )

• at autopsy, heterozygotes with severe wasting symptoms show large pituitary adenocarcinomas (~ 6 mm in diameter) (J:2511)

• consistent with the "two-hit" model proposed by Knudson, such pituitary tumors are shown to arise from cells in which the wild-type allele is absent (J:2511)

• heterozygotes develop intermediate lobe pituitary tumors (J:81082)

increased thyroid tumor incidence ( J:81082 )

• 23/27 heterozygotes show c-cell thyroid tumors

nervous system

increased pituitary gland tumor incidence ( J:2511 , J:81082 )

• at autopsy, heterozygotes with severe wasting symptoms show large pituitary adenocarcinomas (~ 6 mm in diameter) (J:2511)

• consistent with the "two-hit" model proposed by Knudson, such pituitary tumors are shown to arise from cells in which the wild-type allele is absent (J:2511)

• heterozygotes develop intermediate lobe pituitary tumors (J:81082)

Allelic Composition	Rb1^tm1Tyj/Rb1⁺
Genetic Background	involves: 129S2/SvPas * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)

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

mortality/aging

premature death ( J:133299 )

• median lifespan is 372 days compared to 546 days for Men1^tm1.1Ctre heterozygotes

neoplasm

increased pheochromocytoma incidence ( J:133299 )

• in 40% of mice

increased pituitary adenohypophysis tumor incidence ( J:133299 )

• mice exhibit tumors of the pituitary anterior lobe (42%)

• however, no parathyroid adenomas are observed

increased pituitary melanotroph tumor incidence ( J:133299 )

• all mice exhibit tumors of the pituitary intermediate lobe

increased thyroid C-cell carcinoma incidence ( J:133299 )

• all mice exhibit metastic thyroid C-cell carcinomas

increased metastatic potential ( J:133299 )

• 60% of mice exhibit lung metastasis

increased lung tumor incidence ( J:133299 )

• in 60% of mice

endocrine/exocrine glands

increased pheochromocytoma incidence ( J:133299 )

• in 40% of mice

increased pituitary adenohypophysis tumor incidence ( J:133299 )

• mice exhibit tumors of the pituitary anterior lobe (42%)

• however, no parathyroid adenomas are observed

increased pituitary melanotroph tumor incidence ( J:133299 )

• all mice exhibit tumors of the pituitary intermediate lobe

increased thyroid C-cell carcinoma incidence ( J:133299 )

• all mice exhibit metastic thyroid C-cell carcinomas

respiratory system

increased lung tumor incidence ( J:133299 )

• in 60% of mice

nervous system

increased pituitary adenohypophysis tumor incidence ( J:133299 )

• mice exhibit tumors of the pituitary anterior lobe (42%)

• however, no parathyroid adenomas are observed

increased pituitary melanotroph tumor incidence ( J:133299 )

• all mice exhibit tumors of the pituitary intermediate lobe

Allelic Composition	Rb1^tm1Brd/Rb1⁺
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Brd mutation (0 available); any Rb1 mutation (107 available)

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

neoplasm

neoplasm ( J:2516 , J:79648 )

• surprisingly, none of >100 heterozygotes studied show any macroscopic signs of retinoblastoma relative to wild-type mice (J:2516)

• survival of 65 diet restricted heterozygous males is almost identical to that of 67 heterozygous males fed ad libitum (J:79648)

• surprisingly, 40-50% reductions in dietary intake, relative to an ad libitum group, initiated on either P28 or P42 have minimal to no effect on either the frequency or growth of pituitary tumors either during the latency period (P224) or at the time of natural death (J:79648)

increased pituitary adenoma incidence ( J:17434 )

• at >8 months of age, 90% of heterozygotes display signs of pituitary tumors as a "wasting" syndrome; both sexes are susceptible to tumor development

• in young heterozygotes, foci of anaplasia or micro-tumors arise from the intermediate lobe and outgrow toward the neuronal lobe of pituitary glands

• multiple foci are frequently observed in the tiny intermediate lobe of the pituitary gland; on average, 2.2. tumors devepo per intermediate lobe

• in heterozygotes, tumor tissues invariably lose expression of full-length protein due to loss of the remaining wild-type allele

• in heterozygotes, tumor incidence increases with age, with a 21% predisposition at the age of <6 months, >50% at 6-8 months, and 100% at 10 months; the earliest tumor was detected at 2 months

increased metastatic potential ( J:17434 )

• at an advanced stage, pituitary tumors often infiltrate other tissues e.g. hypothalamus, optic nerved, pons, cerebellum, third ventricle, meninges and subarachnoid space

• distal metastasis to the cervical lymph nodes and spinal cord is also detected

increased brain tumor incidence ( J:2516 )

• heterozygotes develop brain tumors at the ages of 4, 7, 8 and 12 months; such tumors are found to arise from cells in which the wild-type allele is absent

endocrine/exocrine glands

abnormal neuroendocrine gland morphology ( J:17434 )

• in heterozygotes, tumor cells appear to exhibit phenotypes of neuroendocrine cells (neuroendocrine neoplasia)

increased pituitary adenoma incidence ( J:17434 )

• at >8 months of age, 90% of heterozygotes display signs of pituitary tumors as a "wasting" syndrome; both sexes are susceptible to tumor development

• in young heterozygotes, foci of anaplasia or micro-tumors arise from the intermediate lobe and outgrow toward the neuronal lobe of pituitary glands

• multiple foci are frequently observed in the tiny intermediate lobe of the pituitary gland; on average, 2.2. tumors devepo per intermediate lobe

• in heterozygotes, tumor tissues invariably lose expression of full-length protein due to loss of the remaining wild-type allele

• in heterozygotes, tumor incidence increases with age, with a 21% predisposition at the age of <6 months, >50% at 6-8 months, and 100% at 10 months; the earliest tumor was detected at 2 months

growth/size/body

increased body mass index ( J:79648 )

• heterozygotes exhibit a 10% increase in body mass relative to wild-type; although this change is reproducible, no excess accumulation of fat is observed

cachexia ( J:17434 )

• heterozygotes bearing large pituitary tumors (~7 mm in diameter) exhibit a severe wasting syndrome

obese ( J:17434 )

• ~3% of tumor-bearing heterozygotes are obese, probably as a result of elevated ACTH levels

nervous system

increased pituitary adenoma incidence ( J:17434 )

• at >8 months of age, 90% of heterozygotes display signs of pituitary tumors as a "wasting" syndrome; both sexes are susceptible to tumor development

• in young heterozygotes, foci of anaplasia or micro-tumors arise from the intermediate lobe and outgrow toward the neuronal lobe of pituitary glands

• multiple foci are frequently observed in the tiny intermediate lobe of the pituitary gland; on average, 2.2. tumors devepo per intermediate lobe

• in heterozygotes, tumor tissues invariably lose expression of full-length protein due to loss of the remaining wild-type allele

• in heterozygotes, tumor incidence increases with age, with a 21% predisposition at the age of <6 months, >50% at 6-8 months, and 100% at 10 months; the earliest tumor was detected at 2 months

increased brain tumor incidence ( J:2516 )

• heterozygotes develop brain tumors at the ages of 4, 7, 8 and 12 months; such tumors are found to arise from cells in which the wild-type allele is absent

Allelic Composition	Rb1^tm1.2Gfk/Rb1⁺
Genetic Background	involves: 129T2/SvEms * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1.2Gfk mutation (0 available); any Rb1 mutation (107 available)

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

mortality/aging

decreased tumor-free survival time ( J:108628 )

• start to die with pituitary tumors around 9 months of age

neoplasm

increased tumor incidence ( J:108628 )

• pituitary tumors result in deaths starting around 9 months of age

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prkar1a^tm1.2Lsk mutation (1 available); any Prkar1a mutation (19 available)
Rb1^tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Col1a1-cre)1Kry mutation (2 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (235 available)

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

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

Allelic Composition	Rb1^tm2Brn/Rb1⁺ Trp53^tm1Brn/Trp53^tm1Brn 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:
Rb1^tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Tg(Col1a1-cre)1Kry mutation (2 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (235 available)

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

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

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sor^{tm1(CAG-MYCN,-luc)Jhsc} mutation (0 available); any Gt(ROSA)26Sor mutation (997 available)
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (86 available)
Rb1^tm2Brn 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

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

• 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

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

• 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

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

Allelic Composition	Rb1^tm3Tyj/Rb1⁺ Sox2^tm4.1Skn/Sox2^tm4.1Skn Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic Background	involves: 129 * C57BL/6 * CD-1

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm3Tyj mutation (10 available); any Rb1 mutation (107 available)
Sox2^tm4.1Skn mutation (1 available); any Sox2 mutation (56 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (235 available)

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

mortality/aging

increased tumor-free survival time ( J:318885 )

• tumor free survival time is increased compared to mutant mice wild-type for Sox2

neoplasm

decreased osteosarcoma incidence ( J:318885 )

• compared to mutant mice wild-type for Sox2

• tumors are uniformly Sox2 positive

skeleton

decreased osteosarcoma incidence ( J:318885 )

• compared to mutant mice wild-type for Sox2

• tumors are uniformly Sox2 positive

Allelic Composition	Rb1^tm3Tyj/Rb1⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic Background	involves: 129 * C57BL/6 * CD-1

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm3Tyj mutation (10 available); any Rb1 mutation (107 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (235 available)

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

mortality/aging

decreased tumor-free survival time ( J:318885 )

• decreased tumor free survival time

neoplasm

increased osteosarcoma incidence ( J:318885 )

skeleton

increased osteosarcoma incidence ( J:318885 )

Allelic Composition	Rb1^tm3Tyj/Rb1⁺ Sox2^tm4.1Skn/Sox2⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic Background	involves: 129 * C57BL/6 * CD-1

Find Mice

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

mortality/aging

increased tumor-free survival time ( J:318885 )

• tumor free survival time is increased compared to mutant mice wild-type for Sox2

neoplasm

decreased osteosarcoma incidence ( J:318885 )

• compared to mutant mice wild-type for Sox2

• tumors are uniformly Sox2 positive

skeleton

decreased osteosarcoma incidence ( J:318885 )

• compared to mutant mice wild-type for Sox2

• tumors are uniformly Sox2 positive

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm2Brn mutation (3 available); any Rb1 mutation (107 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (235 available)

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

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

Allelic Composition	Rb1^tm3Tyj/Rb1⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic Background	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N

Find Mice

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

mortality/aging

premature death ( J:136693 )

• die from around 125 to 260 days of age

neoplasm

increased metastatic potential ( J:136693 )

• tumors show metastasis, most frequently to the lung and then the liver

increased osteosarcoma incidence ( J:136693 )

• develop osteosarcomas at around 4 months of age with 100% penetrance and average latency of 158 days of age

skeleton

increased osteosarcoma incidence ( J:136693 )

• develop osteosarcomas at around 4 months of age with 100% penetrance and average latency of 158 days of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteosarcoma		DOID:3347	OMIM:259500	J:136693

Allelic Composition	Rb1^tm3Tyj/Rb1⁺ Trp53^tm1Brn/Trp53⁺ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic Background	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N

Find Mice

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

mortality/aging

premature death ( J:136693 )

• about 70% survival at 400 days of age, with some mice starting to die around 150 days of age

neoplasm

increased metastatic potential ( J:136693 )

• tumors show metastasis, most frequently to the lung and then the liver

increased osteosarcoma incidence ( J:136693 )

• develop osteosarcomas with a shortened latency (average of 198 days) and increased penetrance (30%) compared to single Trp53 heterozygotes

skeleton

increased osteosarcoma incidence ( J:136693 )

• develop osteosarcomas with a shortened latency (average of 198 days) and increased penetrance (30%) compared to single Trp53 heterozygotes

Allelic Composition	Rb1^tm1Brn/Rb1⁺ X/Tg(Pomc-FLP)1bBrn
Genetic Background	involves: 129P2/OlaHsd * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Brn mutation (1 available); any Rb1 mutation (107 available)
Tg(Pomc-FLP)1bBrn mutation (0 available)

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

endocrine/exocrine glands

pituitary intermediate lobe hyperplasia ( J:48860 )

• at 12 weeks in some mice

nervous system

pituitary intermediate lobe hyperplasia ( J:48860 )

• at 12 weeks in some mice

Allelic Composition	Rb1^tm1Brn/Rb1⁺ Tg(Pomc-FLP)1aBrn/0
Genetic Background	involves: 129P2/OlaHsd * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Brn mutation (1 available); any Rb1 mutation (107 available)
Tg(Pomc-FLP)1aBrn mutation (0 available)

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

nervous system

abnormal pituitary intermediate lobe morphology ( J:48860 )

• at 6 and 12 weeks, mice exhibit atypical lesions in the intermediate lobe of the pituitary gland unlike in Rb1^tm1Brn homozygotes

increased pituitary adenoma incidence ( J:48860 )

• mice develop pituitary adenomas with an average latency of 9 months

• tumors exhibit hyperproliferation

neoplasm

increased pituitary adenoma incidence ( J:48860 )

• mice develop pituitary adenomas with an average latency of 9 months

• tumors exhibit hyperproliferation

endocrine/exocrine glands

abnormal pituitary intermediate lobe morphology ( J:48860 )

• at 6 and 12 weeks, mice exhibit atypical lesions in the intermediate lobe of the pituitary gland unlike in Rb1^tm1Brn homozygotes

increased pituitary adenoma incidence ( J:48860 )

• mice develop pituitary adenomas with an average latency of 9 months

• tumors exhibit hyperproliferation

Allelic Composition	E2f1^tm1Njd/E2f1^tm1Njd Rb1^tm1Tyj/Rb1⁺
Genetic Background	either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
E2f1^tm1Njd mutation (1 available); any E2f1 mutation (26 available)
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)

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

mortality/aging

premature death ( J:47108 )

• increased survival relative to Rb1^tm1Tyj heterozygotes, 15.2 months on a 129 background and up to 17 months on a mixed background

neoplasm

increased pituitary gland tumor incidence ( J:47108 )

• only about 62% develop pituitary tumors

• pituitary tumors are smaller than Rb1^tm1Tyj heterozygotes but histologically indistinguishable

increased thyroid adenoma incidence ( J:47108 )

• fewer thyroid C-cell adenomas than in Rb1^tm1Tyj heterozygotes

increased hemangioma incidence ( J:47108 )

endocrine/exocrine glands

adrenal medulla hyperplasia ( J:47108 )

abnormal thyroid gland morphology ( J:47108 )

• thyroid gland degeneration after 14 months of age

increased pituitary gland tumor incidence ( J:47108 )

• only about 62% develop pituitary tumors

• pituitary tumors are smaller than Rb1^tm1Tyj heterozygotes but histologically indistinguishable

increased thyroid adenoma incidence ( J:47108 )

• fewer thyroid C-cell adenomas than in Rb1^tm1Tyj heterozygotes

reproductive system

uterine hemorrhage ( J:47108 )

cardiovascular system

uterine hemorrhage ( J:47108 )

nervous system

increased pituitary gland tumor incidence ( J:47108 )

• only about 62% develop pituitary tumors

• pituitary tumors are smaller than Rb1^tm1Tyj heterozygotes but histologically indistinguishable

Allelic Composition	E2f1^tm1Njd/E2f1⁺ Rb1^tm1Tyj/Rb1⁺
Genetic Background	either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)

Find Mice

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

mortality/aging

premature death ( J:47108 )

• increased survival relative to Rb1^tm1Tyj heterozygotes, 11.6 months on a 129 background and up to 12.6 months on a mixed background

neoplasm

increased tumor incidence ( J:47108 )

• develop grossly detectable pituitary tumors

increased thyroid adenoma incidence ( J:47108 )

• fewer thyroid C-cell adenomas than in Rb1^tm1Tyj heterozygotes

endocrine/exocrine glands

increased thyroid adenoma incidence ( J:47108 )

• fewer thyroid C-cell adenomas than in Rb1^tm1Tyj heterozygotes

Allelic Composition	Rb1^tm1Fad/Rb1⁺ Tg(KRT14-HPV16E7)2304Plam/0
Genetic Background	involves: 129 * C57BL/6 * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Fad mutation (1 available); any Rb1 mutation (107 available)
Tg(KRT14-HPV16E7)2304Plam mutation (1 available)

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

cellular

cellular phenotype ( J:101623 )

N	• after exposure to 5 Gy of ionizing radiation skin cells display normal cell cycle arrest unlike in mice hemizygous for Tg(KRT14-HPV16E7)2304Plam alone

integument

abnormal epidermis suprabasal layer morphology ( J:101623 )

• thickness of the spinous suprabasal cell layer is increased 30-50%; however, the thickness of the keratin 10- and filaggrin-positive layers is normal

• mice have normal gross skin morphology, normal growth and no signs of epidermal hyperplasia unlike in mice hemizygous for Tg(KRT14-HPV16E7)2304Plam alone

Allelic Composition	Msh2^tm1Whl/Msh2^tm1Whl Rb1^tm1Brd/Rb1⁺
Genetic Background	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msh2^tm1Whl mutation (0 available); any Msh2 mutation (95 available)
Rb1^tm1Brd mutation (0 available); any Rb1 mutation (107 available)

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

mortality/aging

premature death ( J:79016 )

• life span is extended compared to mice homozygous for the Msh2 allele alone but shorter than that of mice heterozygous for the Rb allele alone

neoplasm

abnormal tumor morphology ( J:79016 )

• microsatellite instability is seen in all lymphomas and intestinal tumors but not in other tumor types

increased tumor incidence ( J:79016 )

• some mice develop soft tissue tumors (myxoid fibrosarcoma, hemangiosarcoma, and hemangioendothelioma)

increased gastrointestinal tumor incidence ( J:79016 )

• most mice develop gastrointestinal tumors

increased pheochromocytoma incidence ( J:79016 )

• seen in most mice

increased pituitary adenohypophysis tumor incidence ( J:79016 )

• some mice develop tumors of the pituitary anterior lobe

increased pituitary melanotroph tumor incidence ( J:79016 )

• all mice develop melanotroph tumors of the pituitary

increased lymphoblastic lymphoma incidence ( J:79016 )

• apoptosis of lymphoma cells is increased compared to cells from mice homozygous for the Msh2 allele alone

increased thyroid C-cell carcinoma incidence ( J:79016 )

• most mice develop C cell thyroid carcinomas

increased skin tumor incidence ( J:79016 )

hematopoietic system

abnormal definitive hematopoiesis ( J:79016 )

• ability of hematopoietic cells to rescue lethally irradiated mice is impaired although not as badly as for cells from double homozygous mice

integument

increased skin tumor incidence ( J:79016 )

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:79016 )

• most mice develop gastrointestinal tumors

endocrine/exocrine glands

increased pheochromocytoma incidence ( J:79016 )

• seen in most mice

increased pituitary adenohypophysis tumor incidence ( J:79016 )

• some mice develop tumors of the pituitary anterior lobe

increased pituitary melanotroph tumor incidence ( J:79016 )

• all mice develop melanotroph tumors of the pituitary

increased lymphoblastic lymphoma incidence ( J:79016 )

• apoptosis of lymphoma cells is increased compared to cells from mice homozygous for the Msh2 allele alone

increased thyroid C-cell carcinoma incidence ( J:79016 )

• most mice develop C cell thyroid carcinomas

nervous system

increased pituitary adenohypophysis tumor incidence ( J:79016 )

• some mice develop tumors of the pituitary anterior lobe

increased pituitary melanotroph tumor incidence ( J:79016 )

• all mice develop melanotroph tumors of the pituitary

Allelic Composition	Rb1^tm1Tyj/Rb1⁺ Trim27^{Gt(XP0484)Wtsi}/Trim27^{Gt(XP0484)Wtsi}
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Trim27^{Gt(XP0484)Wtsi} mutation (0 available); any Trim27 mutation (32 available)

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

neoplasm

increased tumor incidence ( J:189317 )

• as in Rb1^tm1Tyj heterozygotes

increased pituitary gland tumor incidence ( J:189317 )

• as in Rb1^tm1Tyj heterozygotes

increased thyroid tumor incidence ( J:189317 )

• as in Rb1^tm1Tyj heterozygotes

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:189317 )

• as in Rb1^tm1Tyj heterozygotes

increased thyroid tumor incidence ( J:189317 )

• as in Rb1^tm1Tyj heterozygotes

nervous system

increased pituitary gland tumor incidence ( J:189317 )

• as in Rb1^tm1Tyj heterozygotes

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Rb1^tm1Tyj/Rb1⁺ Tg(Rb1)1Blg/0
Genetic Background	involves: 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Tg(Rb1)1Blg mutation (0 available)

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

skeleton

abnormal xiphoid process morphology ( J:65679 )

• at E17.5

Allelic Composition	Men1^tm1.1Ctre/Men1⁺ Rb1^tm1Tyj/Rb1⁺
Genetic Background	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Men1^tm1.1Ctre mutation (2 available); any Men1 mutation (40 available)
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)

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

mortality/aging

premature death ( J:133299 )

• median lifespan is 402 days compared to 546 days for Men1^tm1.1Ctre heterozygotes

neoplasm

increased adrenal gland tumor incidence ( J:133299 )

• adrenal cortical tumor (10% of mice)

increased pheochromocytoma incidence ( J:133299 )

• in 45% of mice

increased pancreas tumor incidence ( J:133299 )

• 55% of mice exhibit pancreatic islet tumors

increased parathyroid gland tumor incidence ( J:133299 )

• 50% of mice exhibit parathyroid gland tumors

increased pituitary adenohypophysis tumor incidence ( J:133299 )

• mice exhibit pituitary anterior lobe tumors (40% of mice)

increased pituitary melanotroph tumor incidence ( J:133299 )

• pituitary intermediate lobe tumors (96% of mice)

increased thyroid C-cell carcinoma incidence ( J:133299 )

• mice exhibit thyroid C-cell carcinomas (96%)

increased metastatic potential ( J:133299 )

• metastasis in the lungs (70% of mice)

nervous system

increased pituitary adenohypophysis tumor incidence ( J:133299 )

• mice exhibit pituitary anterior lobe tumors (40% of mice)

increased pituitary melanotroph tumor incidence ( J:133299 )

• pituitary intermediate lobe tumors (96% of mice)

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:133299 )

• adrenal cortical tumor (10% of mice)

increased pheochromocytoma incidence ( J:133299 )

• in 45% of mice

increased pancreas tumor incidence ( J:133299 )

• 55% of mice exhibit pancreatic islet tumors

increased parathyroid gland tumor incidence ( J:133299 )

• 50% of mice exhibit parathyroid gland tumors

increased pituitary adenohypophysis tumor incidence ( J:133299 )

• mice exhibit pituitary anterior lobe tumors (40% of mice)

increased pituitary melanotroph tumor incidence ( J:133299 )

• pituitary intermediate lobe tumors (96% of mice)

increased thyroid C-cell carcinoma incidence ( J:133299 )

• mice exhibit thyroid C-cell carcinomas (96%)

Allelic Composition	Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael Rb1^tm1Tyj/Rb1⁺
Genetic Background	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kdm5a^tm1.1Kael mutation (1 available); any Kdm5a mutation (76 available)
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)

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

mortality/aging

premature death ( J:175625 )

• median survival is 72 weeks

neoplasm

increased pituitary gland tumor incidence ( J:175625 )

• in 8 of 10 mice; 3 of 4 with intermediate lobe origins and 1 in 4 anterior lobe origins

increased thyroid tumor incidence ( J:175625 )

• in 8 of 10 mice

nervous system

increased pituitary gland tumor incidence ( J:175625 )

• in 8 of 10 mice; 3 of 4 with intermediate lobe origins and 1 in 4 anterior lobe origins

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:175625 )

• in 8 of 10 mice; 3 of 4 with intermediate lobe origins and 1 in 4 anterior lobe origins

increased thyroid tumor incidence ( J:175625 )

• in 8 of 10 mice

Allelic Composition	Kdm5a^tm1.1Kael/Kdm5a⁺ Rb1^tm1Tyj/Rb1⁺
Genetic Background	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

Find Mice

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

neoplasm

increased pituitary gland tumor incidence ( J:175625 )

• in 15 of 18 mice; 9 of 12 with intermediate lobe origins, 1 in 12 anterior lobe origins, and 2 of 12 intermediate and anterior lobe origins

increased thyroid tumor incidence ( J:175625 )

• in 16 of 18 mice

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:175625 )

• in 15 of 18 mice; 9 of 12 with intermediate lobe origins, 1 in 12 anterior lobe origins, and 2 of 12 intermediate and anterior lobe origins

increased thyroid tumor incidence ( J:175625 )

• in 16 of 18 mice

nervous system

increased pituitary gland tumor incidence ( J:175625 )

• in 15 of 18 mice; 9 of 12 with intermediate lobe origins, 1 in 12 anterior lobe origins, and 2 of 12 intermediate and anterior lobe origins

Allelic Composition	Rb1^tm1Tyj/Rb1⁺ Tg(Th-MYCN)41Waw/0
Genetic Background	involves: 129S2/SvPas * BALB/c * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Tg(Th-MYCN)41Waw mutation (2 available)

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

neoplasm

increased neuroblastoma incidence ( J:41126 )

• mutants exhibit a decreased latency and an increased incidence of tumors compared to single hemizygous Tg(Th-MYCN)41Waw mice, such that about 75% of mutants develop neuroblastomas by 10 months of age compared to 40% of single hemizygous Tg(Th-MYCN)41Waw mice

nervous system

increased neuroblastoma incidence ( J:41126 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:41106

Allelic Composition	Rb1^tm1Tyj/Rb1⁺ Trp53^tm1Tyj/Trp53⁺
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Trp53^tm1Tyj mutation (12 available); any Trp53 mutation (235 available)

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

mortality/aging

premature death ( J:19542 )

• the mean age of survival of double heterozygotes is slightly reduced relative to mice heterozygous for Rb1^tm1Tyj alone (9 months vs 11 months)

neoplasm

abnormal tumor morphology ( J:19542 )

• in nearly all double heterozygotes with pituitary and thyroid tumors, the wild-type allele of Rb1 is lost whereas the wild-type allele of Trp53 is retained

increased tumor incidence ( J:19542 )

• one of 7 individual double heterozygotes analyzed displayed a single pinealoblastoma (not detected in single heterozygotes); the wild-type alleles of both Rb1 and Trp53 were lost in this pineal tumor

increased pancreatic islet cell carcinoma incidence ( J:19542 )

• 14% of a total of 14 individual double heterozygotes analyzed displayed islet cell carcinomas (not detected in single heterozygotes)

• notably, the wild-type alleles of both Rb1 and Trp53 were lost in tumors of the islet cells of the pancreas

increased pituitary melanotroph tumor incidence ( J:19542 )

• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe

increased thyroid tumor incidence ( J:19542 )

• ~75% of double heterozygous mice develop medullary thyroid tumors

increased sarcoma incidence ( J:19542 )

• 6% of a total of 67 individual double heterozygotes analyzed displayed anaplastic sarcomas

• such tumors were shown to be more aggressive and arise at an earlier age than those occurring in single Trp53^tm1Tyj heterozygotes

• notably, the wild-type alleles of both Rb1 and Trp53 were lost in these anaplastic sarcomas

increased leiomyosarcoma incidence ( J:19542 )

• one of 7 individual double heterozygotes analyzed displayed a leiomyosarcoma

respiratory system

bronchial epithelial hyperplasia ( J:19542 )

• 8% of a total of 12 individual double heterozygotes analyzed displayed bronchial hyperplasia

muscle

increased leiomyosarcoma incidence ( J:19542 )

• one of 7 individual double heterozygotes analyzed displayed a leiomyosarcoma

endocrine/exocrine glands

increased pancreatic islet cell carcinoma incidence ( J:19542 )

• 14% of a total of 14 individual double heterozygotes analyzed displayed islet cell carcinomas (not detected in single heterozygotes)

• notably, the wild-type alleles of both Rb1 and Trp53 were lost in tumors of the islet cells of the pancreas

increased pituitary melanotroph tumor incidence ( J:19542 )

• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe

increased thyroid tumor incidence ( J:19542 )

• ~75% of double heterozygous mice develop medullary thyroid tumors

nervous system

increased pituitary melanotroph tumor incidence ( J:19542 )

• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe

Allelic Composition	E2f4^tm1Lees/E2f4^tm1Lees Rb1^tm1Tyj/Rb1⁺
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
E2f4^tm1Lees mutation (1 available); any E2f4 mutation (21 available)
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)

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

mortality/aging

premature death ( J:81082 )

• two mutant mice died at early stages (2.7 and 5.4 months) as a result of increased susceptibility to infection, however majority of mutant mice survived at least until the window of lethality of the single heterozygous mutant Rb1 mice and a significant fraction lived to an age comparable to wild-type

neoplasm

decreased tumor incidence ( J:81082 )

• suppressed tumor formation compared to single heterozygous mutant Rb1 mice, with no mutants developing pituitary tumors prior to 16 months of age and significantly lower incidence of pituitary tumors thereafter and only 1/17 mutants developing a c-cell thyroid tumor

immune system

increased susceptibility to infection ( J:81082 )

• two mutant mice died at early stages (2.7 and 5.4 months) as a result of increased susceptibility to infection, however showed no evidence of tumorigenic lesions in these mice

Allelic Composition	E2f4^tm1Lees/E2f4⁺ Rb1^tm1Tyj/Rb1⁺
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

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

mortality/aging

premature death ( J:81082 )

• died by 18 months of age compared to 20-27 months in wild-type

neoplasm

increased pituitary gland tumor incidence ( J:81082 )

• developed pituitary tumors that were comparable to those arising in single heterozygous mutant Rb1 mice with respect to both incidence and size

increased thyroid tumor incidence ( J:81082 )

• developed thyroid tumors that were comparable to those arising in single heterozygous mutant Rb1 mice with respect to both incidence and size

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:81082 )

• developed pituitary tumors that were comparable to those arising in single heterozygous mutant Rb1 mice with respect to both incidence and size

increased thyroid tumor incidence ( J:81082 )

• developed thyroid tumors that were comparable to those arising in single heterozygous mutant Rb1 mice with respect to both incidence and size

nervous system

increased pituitary gland tumor incidence ( J:81082 )

• developed pituitary tumors that were comparable to those arising in single heterozygous mutant Rb1 mice with respect to both incidence and size

Allelic Composition	Rb1^tm1Tyj/Rb1⁺ Rbl1^tm1Tyj/Rbl1^tm1Tyj
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Rbl1^tm1Tyj mutation (1 available); any Rbl1 mutation (60 available)

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

mortality/aging

premature death ( J:34058 )

• females displaying vaginal atresia accumulate fluid in the uterus and die between 4 and 6 months of age

decreased tumor-free survival time ( J:34058 )

• similar to Rb1^tm1Tyj heterozygotes, any surviving mutant mice eventually die of pituitary tumors after 12 months

postnatal lethality, incomplete penetrance ( J:34058 )

• at 1 week of age, mutant pups are obtained at a significantly lower frequency (19%) than expected (25%)

• most mutants die within the first 3 weeks of age, with only about 25% surviving beyond 3 weeks

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:34058 )

• similar to Rb1^tm1Tyj heterozygotes, all surviving mutant mice develop large pituitary adenocarcinomas of the intermediate lobe

growth/size/body

decreased body size ( J:34058 )

• mutant pups become runted several days after birth

decreased body weight ( J:34058 )

• beginning at ~1 week, mutant pups appear severely growth retarded, averaging 50% of the weight of control littermates

• mutants surviving beyond 3 weeks of age gain weight slowly, averaging 70-90% of normal weight at 3 months

postnatal growth retardation ( J:34058 )

• although mutant pups are of approximately uniform size at birth, a number of pups display severe growth retardation, with weight differences persisting for several weeks

distended abdomen ( J:34058 )

• females displaying vaginal atresia have a distended abdomen as a result of fluid accumulation in the uterus

neoplasm

increased pituitary gland tumor incidence ( J:34058 )

• similar to Rb1^tm1Tyj heterozygotes, all surviving mutant mice develop large pituitary adenocarcinomas of the intermediate lobe

reproductive system

abnormal perineum morphology ( J:34058 )

• females displaying vaginal atresia have a distended perineum as a result of fluid accumulation in the uterus

vagina atresia ( J:34058 )

• ~75% of mutant females display vaginal atresia whereas the majority of mutant males surviving beyond 3 weeks of age are fertile and appear normal up to 12 months

• in affected females, the vaginal opening is absent; however, the rest of the reproductive tract appears unaffected

vision/eye

abnormal retina morphology ( J:34058 )

• at 4-6 months, all mutant mice display retinal dysplasia; both eyes are affected in 11 out of 12 mutants

• typically, each eye contains 5-7 individual lesions composed of small white bodies (usually in clusters), indicating retinal pathology

abnormal retina photoreceptor morphology ( J:34058 )

• as early as 4 days after birth, mutant newborns exhibit mild, yet significant, disruptions of the retinal photoreceptor layer

nervous system

increased pituitary gland tumor incidence ( J:34058 )

• similar to Rb1^tm1Tyj heterozygotes, all surviving mutant mice develop large pituitary adenocarcinomas of the intermediate lobe

abnormal retina photoreceptor morphology ( J:34058 )

• as early as 4 days after birth, mutant newborns exhibit mild, yet significant, disruptions of the retinal photoreceptor layer

digestive/alimentary system

abnormal perineum morphology ( J:34058 )

• females displaying vaginal atresia have a distended perineum as a result of fluid accumulation in the uterus

Allelic Composition	Rb1^tm1Tyj/Rb1⁺ Rbl1^tm1Tyj/Rbl1⁺
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

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

mortality/aging

decreased tumor-free survival time ( J:34058 )

• similar to Rb1^tm1Tyj heterozygotes, mice heterozygous for both Rb1^tm1Tyj and Rbl1^tm1Tyj die from tumors in the intermediate lobe of the pituitary gland at ~12 months of age

neoplasm

increased pituitary gland tumor incidence ( J:34058 )

• double heterozygotes develop large pituitary tumors of the intermediate lobe that are comparable to those arising in single Rb1^tm1Tyj heterozygotes with respect to both incidence and size

• such pituitary tumors are shown to arise from cells in which the wild-type allele of Rb1 is absent, whereas the wild-type allele of Rbl1 is retained

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:34058 )

• double heterozygotes develop large pituitary tumors of the intermediate lobe that are comparable to those arising in single Rb1^tm1Tyj heterozygotes with respect to both incidence and size

• such pituitary tumors are shown to arise from cells in which the wild-type allele of Rb1 is absent, whereas the wild-type allele of Rbl1 is retained

nervous system

increased pituitary gland tumor incidence ( J:34058 )

• double heterozygotes develop large pituitary tumors of the intermediate lobe that are comparable to those arising in single Rb1^tm1Tyj heterozygotes with respect to both incidence and size

• such pituitary tumors are shown to arise from cells in which the wild-type allele of Rb1 is absent, whereas the wild-type allele of Rbl1 is retained

Allelic Composition	Rb1^tm1Tyj/Rb1⁺ Tg(S100b-v-erbB)4496Waw/0
Genetic Background	involves: 129S2/SvPas * C57BL/6J * DBA/2J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Tg(S100b-v-erbB)4496Waw mutation (1 available)

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

neoplasm

increased glioma incidence ( J:82649 )

• mice develop gliomas in the same pattern and with the same pathology as in Tg(S100b-v-erbB)4496Waw mice

nervous system

increased glioma incidence ( J:82649 )

• mice develop gliomas in the same pattern and with the same pathology as in Tg(S100b-v-erbB)4496Waw mice

Allelic Composition	Rb1^tm1Brd/Rb1⁺ Rr70^tm1Alb/Rr70⁺
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Brd mutation (0 available); any Rb1 mutation (107 available)
Rr70^tm1Alb mutation (0 available); any Rr70 mutation (0 available)

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

cellular

abnormal DNA methylation ( J:113402 )

abnormal imprinting ( J:113402 )

• 7 of 10 mice lack correct DNA methylation patterns

Allelic Composition	Rb1^tm1Brd/Rb1⁺ Trp53^tm1Brd/Trp53⁺
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Brd mutation (0 available); any Rb1 mutation (107 available)
Trp53^tm1Brd mutation (5 available); any Trp53 mutation (235 available)

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

mortality/aging

premature death ( J:79016 )

• life span is shorter compared to littermates with only a single gene defect

Allelic Composition	Rb1^tm1Tyj/Rb1⁺ Smarca4^tm1Mag/Smarca4⁺
Genetic Background	involves: 129S/Sv * 129S2/SvPas * C57BL/6J * CD-1

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Smarca4^tm1Mag mutation (1 available); any Smarca4 mutation (109 available)

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

mortality/aging

premature death ( J:132091 )

• mice die by 14 months of age due to pituitary tumors

neoplasm

increased pituitary gland tumor incidence ( J:132091 )

• mice develop pituitary tumors with 100% penetrance and median latency period of 12-13 months

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:132091 )

• mice develop pituitary tumors with 100% penetrance and median latency period of 12-13 months

nervous system

increased pituitary gland tumor incidence ( J:132091 )

• mice develop pituitary tumors with 100% penetrance and median latency period of 12-13 months

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