All Phenotypes Rb1<tm1Tyj> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Rb1^tm1Tyj
targeted mutation 1, Tyler Jacks
MGI:1857242

Summary

42 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rb1^tm1Tyj/Rb1^tm1Tyj	involves: 129S2/SvPas	MGI:2166359
hm2	Rb1^tm1Tyj/Rb1^tm1Tyj	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296666
hm3	Rb1^tm1Tyj/Rb1^tm1Tyj	involves: 129S2/SvPas * C57BL/6	MGI:3582488
ht4	Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas	MGI:5614091
ht5	Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296667
ht6	Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * C57BL/6	MGI:3582548
ht7	Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * C57BL/6J	MGI:3839771
ht8	Rb1^tm1Tyj/Rb1^tm2Tyj	chimera involves: 129S2/SvPas * C57BL/6	MGI:3843184
ht9	Rb1^tm1Dwg/Rb1^tm1Tyj	involves: 129/Sv * 129S2/SvPas * C57BL/6	MGI:3618362
cn10	Rb1^tm1Tyj/Rb1^tm2Brn Rbl1^tm1Tyj/Rbl1^tm1Tyj Trp53^tm1Brn/Trp53^tm1Brn Tg(Chx10-EGFP/cre,-ALPP)2Clc/0	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL	MGI:3710238
cn11	Rb1^tm1Tyj/Rb1^tm2Brn Rbl1^tm1Tyj/Rbl1^tm1Tyj Trp53^tm1Brn/Trp53^tm1Tyj Tg(Chx10-EGFP/cre,-ALPP)2Clc/0	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL	MGI:3710239
cn12	Rb1^tm1Tyj/Rb1^tm2Brn Rbl1^tm1Tyj/Rbl1⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Chx10-EGFP/cre,-ALPP)2Clc/0	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL	MGI:3710240
cn13	Rb1^tm1Tyj/Rb1^tm2Brn Rbl1^tm1Tyj/Rbl1⁺ Tg(Chx10-EGFP/cre,-ALPP)2Clc/0	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL	MGI:3710241
cx14	E2f1^tm1Njd/E2f1^tm1Njd Rb1^tm1Tyj/Rb1⁺	either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)	MGI:3840353
cx15	E2f1^tm1Njd/E2f1⁺ Rb1^tm1Tyj/Rb1⁺	either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)	MGI:3840352
cx16	E2f1^tm1Njd/E2f1⁺ Rb1^tm1Tyj/Rb1^tm1Tyj	either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)	MGI:3840351
cx17	E2f1^tm1Njd/E2f1^tm1Njd Rb1^tm1Tyj/Rb1^tm1Tyj	either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)	MGI:3840350
cx18	Apaf1^tm1Mak/Apaf1^tm1Mak Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6	MGI:3699923
cx19	Rb1^tm1Tyj/Rb1⁺ Trim27^{Gt(XP0484)Wtsi}/Trim27^{Gt(XP0484)Wtsi}	involves: 129P2/OlaHsd * C57BL/6	MGI:5446920
cx20	Rb1^tm1Tyj/Rb1^tm1Tyj Trim27^{Gt(XP0484)Wtsi}/Trim27^{Gt(XP0484)Wtsi}	involves: 129P2/OlaHsd * C57BL/6	MGI:5446919
cx21	Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0 Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas	MGI:4420470
cx22	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0	involves: 129S2/SvPas	MGI:4420466
cx23	Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0	involves: 129S2/SvPas	MGI:4420468
cx24	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Rb1^tm1Tyj/Rb1⁺ Tg(Rb1)1Blg/0	involves: 129S2/SvPas	MGI:4420467
cx25	E2f1^tm1Meg/E2f1^tm1Meg Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0	involves: 129S2/SvPas * 129S4/SvJae	MGI:4420469
cx26	Rb1^tm1Tyj/Rb1^tm1Tyj Rbl1^tm1Mru/Rbl1^tm1Mru	involves: 129S2/SvPas * 129S4/SvJae * BALB/c * C57BL/6	MGI:4353990
cx27	Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6	MGI:3699919
cx28	Men1^tm1.1Ctre/Men1⁺ Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:3839773
cx29	Kdm5a^tm1.1Kael/Kdm5a⁺ Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296663
cx30	Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296664
cx31	Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael Rb1^tm1Tyj/Rb1^tm1Tyj	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296668
cx32	Kdm5a^tm1.1Kael/Kdm5a⁺ Rb1^tm1Tyj/Rb1^tm1Tyj	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296665
cx33	Rb1^tm1Tyj/Rb1⁺ Tg(Th-MYCN)41Waw/0	involves: 129S2/SvPas * BALB/c * C57BL/6J	MGI:5009553
cx34	Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0	involves: 129S2/SvPas * C57BL/6	MGI:3699732
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⁺ Trp53^tm1Tyj/Trp53⁺	involves: 129S2/SvPas * C57BL/6	MGI:3582787
cx38	E2f4^tm1Lees/E2f4^tm1Lees Rb1^tm1Tyj/Rb1⁺	involves: 129S2/SvPas * C57BL/6	MGI:3582517
cx39	Rb1^tm1Tyj/Rb1^tm1Tyj Rbl1^tm1Tyj/Rbl1^tm1Tyj	involves: 129S2/SvPas * C57BL/6	MGI:3582586
cx40	Rb1^tm1Tyj/Rb1⁺ Rbl1^tm1Tyj/Rbl1⁺	involves: 129S2/SvPas * C57BL/6	MGI:3582618
cx41	Rb1^tm1Tyj/Rb1⁺ Tg(S100b-v-erbB)4496Waw/0	involves: 129S2/SvPas * C57BL/6J * DBA/2J * FVB/N	MGI:3822322
cx42	Rb1^tm1Tyj/Rb1⁺ Smarca4^tm1Mag/Smarca4⁺	involves: 129S/Sv * 129S2/SvPas * C57BL/6J * CD-1	MGI:5763442

Allelic Composition	Rb1^tm1Tyj/Rb1^tm1Tyj
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 (111 available)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:105548 )

• live homozygotes are rarely recovered at E15.5 and never at E16.5

hematopoietic system

abnormal macrophage differentiation ( J:105548 )

• fetal liver macrophages exhibit defects in differentiation, as indicated by small size, lack of extensive cytoplasmic projections, and weak staining for a mature macrophage marker

abnormal erythropoiesis ( J:105548 )

• significant decrease in the percentage of enucleated erythrocytes, indicating defective erythrocyte maturation

increased nucleated erythrocyte cell number ( J:81643 )

• at E13.5, peripheral blood smears contain predominantly nucleated erythrocytes

liver/biliary system

liver hypoplasia ( J:81643 )

• at E13.5 liver cellularity is decreased and the level of apoptosis is increased

nervous system

increased neuron apoptosis ( J:81643 )

• at E13.5, apoptosis is increased in the brain, dorsal root ganglia, and trigeminal ganglia

abnormal neuron differentiation ( J:81643 )

• at E13.5, proliferation is increased in the brain, dorsal root ganglia, and trigeminal ganglia

abnormal fourth ventricle morphology ( J:105548 )

• detect ectopic mitosis and apoptosis in the intermediate zones of the fourth ventricle

abnormal third ventricle morphology ( J:105548 )

• detect ectopic mitosis and apoptosis in the intermediate zones of the third ventricle

abnormal trigeminal ganglion morphology ( J:105548 )

• detect ectopic mitosis and apoptosis in the trigeminal ganglia

abnormal dorsal root ganglion morphology ( J:105548 )

• detect ectopic mitosis and apoptosis in the dorsal root ganglia

vision/eye

increased lens fiber apoptosis ( J:105548 )

• apoptosis is detected in the lens fiber compartment that is not seen in wild-type

abnormal lens development ( J:81643 )

• at E13.5, ectopic proliferating cells are seen in the interior of the lens and increased apoptosis is seen

abnormal lens fiber morphology ( J:105548 )

• detect ectopic mitoses in the lens fiber compartment that is not seen in wild-type

• lens fiber cells are disorganized

homeostasis/metabolism

hypoxia ( J:81643 )

• expression of hypoxia-inducible genes is increased in the central nervous system at E13.5

cellular

abnormal cell cycle ( J:105548 )

• MEFs exhibit an increase in the fraction of cells in the S and G2/M phases of the cell cycle

abnormal cell cycle checkpoint function ( J:105548 )

• MEFs fail to efficiently trigger G1/S cell cycle arrest in response to DNA damage

increased lens fiber apoptosis ( J:105548 )

• apoptosis is detected in the lens fiber compartment that is not seen in wild-type

increased neuron apoptosis ( J:81643 )

• at E13.5, apoptosis is increased in the brain, dorsal root ganglia, and trigeminal ganglia

abnormal macrophage differentiation ( J:105548 )

• fetal liver macrophages exhibit defects in differentiation, as indicated by small size, lack of extensive cytoplasmic projections, and weak staining for a mature macrophage marker

abnormal neuron differentiation ( J:81643 )

• at E13.5, proliferation is increased in the brain, dorsal root ganglia, and trigeminal ganglia

increased fibroblast proliferation ( J:105548 )

• MEFs cultured at confluence exhibit an increase in cell proliferation compared to wild-type MEFs

embryo

decreased embryo size ( J:105548 )

abnormal placenta labyrinth morphology ( J:105548 )

• normal labyrinth architecture is disrupted

• the porous appearance of the labyrinth layer is absent

abnormal placental transport ( J:105548 )

• exhibit defective placental transport as indicated by a 7.2% reduction of the essential fatty acid linoleic acid, arachidonic acid and docosahexaenoic acid in E14.5 embryos relative to wild-type

growth/size/body

decreased embryo size ( J:105548 )

immune system

abnormal macrophage differentiation ( J:105548 )

• fetal liver macrophages exhibit defects in differentiation, as indicated by small size, lack of extensive cytoplasmic projections, and weak staining for a mature macrophage marker

integument

pallor ( J:105548 )

Allelic Composition	Rb1^tm1Tyj/Rb1^tm1Tyj
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 (111 available)

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

mortality/aging

embryonic lethality, complete penetrance ( J:175625 )

cellular

abnormal cell differentiation ( J:175625 )

• mouse embryonic fibroblasts transfected with a vector expressing Myod1 (MyoD) fail to differentiate into myocytes unlike similarly treated wild-type cells

• transfection with a vector expressing Myhc partially rescues myocyte differentiation

Allelic Composition	Rb1^tm1Tyj/Rb1^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 (111 available)

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:2511 , J:81082 )

• homozygous mutant embryos die between E14.5 and E15.5 (J:2511)

hematopoietic system

anemia ( J:2511 )

• at E13.5, homozygotes are severely pale relative to wild-type embryos

abnormal erythrocyte morphology ( J:2511 )

• in vitro, mutant erythroid precursors fail to reach end-stage differentiation: small hemaglobinized colonies from mutant mice are pale and contain increased numbers of small late normoblast-like cells instead of enucleated (mature) erythrocytes

• similarly, mutant large erythroid colonies are pale, with <5% enucleated erythrocytes relative to wild-type (45%)

abnormal erythropoiesis ( J:2511 )

• at E13.5, homozygotes display impaired definitive erythropoiesis and fail to produce sufficient numbers of mature erythrocytes, resulting in hypoxia and eventually death

low mean erythrocyte cell number ( J:2511 )

• at E13.5, wild-type embryos contain on average 45% enucleated, definitive erythrocytes; in contrast, mutant embryos only contain 6.8% enucleated cells

liver/biliary system

abnormal liver morphology ( J:2511 )

• at E13.5, mutant livers appear lacy and largely acellular; in contrast, wild-type livers are densely packed with cells (90% of which are of erythroid lineage)

small liver ( J:2511 )

• at E13.5, homozygotes display a slight reduction in liver size

homeostasis/metabolism

pericardial edema ( J:2511 )

• at E13.5, homozygotes display significant edema, particularly in the pericardial space

skin edema ( J:2511 )

• at E13.5, edema results in damage of the dermis and underlying mesenchyme

• however, most non-hematopoietic tissues remain unaffected until death (~E14.5)

cardiovascular system

pericardial edema ( J:2511 )

• at E13.5, homozygotes display significant edema, particularly in the pericardial space

nervous system

nervous system phenotype ( J:92520 )

N	• normal numbers of primary neurospheres are produced from cultured E10 telencephalic neuroepithelia

increased neuron apoptosis ( J:2511 )

• at E12.5, mutant embryos exhibit increased neuronal apoptosis in the spinal cord, dorsal root ganglia and parts of the hindbrain

• neuronal cell death occurs prior to the manifestation of the erythropoietic defect, and does not appear to be a secondary effect of anemia-induced hypoxia

vision/eye

vision/eye phenotype ( J:2511 )

N	• at E13.5, homozygotes display normal retinal development

cellular

increased apoptosis ( J:37145 )

• at E13.5, TUNEL analysis indicates a significant increase in apoptotic nuclei throughout the mutant nervous system (esp. dorsal ganglia), in skeletal muscle precursor cells (e.g. tongue myoblasts), lens, and to a lesser extent in liver

• in contrast, no significant increase in apoptosis is noted in the mutant lung or cardiac muscles

increased neuron apoptosis ( J:2511 )

• at E12.5, mutant embryos exhibit increased neuronal apoptosis in the spinal cord, dorsal root ganglia and parts of the hindbrain

• neuronal cell death occurs prior to the manifestation of the erythropoietic defect, and does not appear to be a secondary effect of anemia-induced hypoxia

increased cell proliferation ( J:81082 )

• MEFs largely fail to arrest in response to confluent growth and ~40% of the cells enter S phase

behavior/neurological

hunched posture ( J:37145 )

• at E13.5, 7 of 8 homozygotes display a hunchback posture

skeleton

abnormal cartilage morphology ( J:37145 )

• at E13.5, 7 of 8 homozygotes display a reduced cartilaginous frame (perichondrium) relative to wild-type mice

integument

skin edema ( J:2511 )

• at E13.5, edema results in damage of the dermis and underlying mesenchyme

• however, most non-hematopoietic tissues remain unaffected until death (~E14.5)

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 (111 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 (111 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 (111 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 (111 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^tm1Tyj/Rb1^tm2Tyj
Genetic Background	chimera 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 (111 available)
Rb1^tm2Tyj mutation (0 available); any Rb1 mutation (111 available)

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

growth/size/body

cachexia ( J:59268 )

• display severe wasting and become moribund by 3-4 months

neoplasm

increased pituitary adenoma incidence ( J:59268 )

• severe adenocarcenomas by 3-4 months of age in chimeric mice

• derived from the intermediate lobe

preneoplasia ( J:59268 )

• hyperchromatic cells are found in the adrenal medulla of chimeric mice indicating neoplastic lesions

nervous system

nervous system phenotype ( J:59268 )

N	• examined in chimeric mice

increased pituitary adenoma incidence ( J:59268 )

• severe adenocarcenomas by 3-4 months of age in chimeric mice

• derived from the intermediate lobe

abnormal Purkinje cell morphology ( J:59268 )

• cells with enlarged nuclei

ectopic Purkinje cell ( J:59268 )

• displaced Purkinje cells

thin cerebellar granule layer ( J:59268 )

liver/biliary system

abnormal hepatocyte morphology ( J:59268 )

• abnormally large nuclei in chimeric mice

vision/eye

vision/eye phenotype ( J:59268 )

N	• examined in chimeric mice • no retinoblastomas • normal retinal architecture

cataract ( J:59268 )

• in all mice examined

• evidence of cataracts when eyes first open at 1 week of age

• characterized by a posterior migration of the lens epithelium

• associated with bladder cell formation and sometimes with calcification

• lens of newborns highly disorganized with many pyknotic cells

endocrine/exocrine glands

increased pituitary adenoma incidence ( J:59268 )

• severe adenocarcenomas by 3-4 months of age in chimeric mice

• derived from the intermediate lobe

Allelic Composition	Rb1^tm1Dwg/Rb1^tm1Tyj
Genetic Background	involves: 129/Sv * 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Dwg mutation (0 available); any Rb1 mutation (111 available)
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (111 available)

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:105548 )

• survive as long as homozygous Rb1^tm1Dwg mice, with 2 of 18 dead at E15.5 and 4 of 7 dead at E17.5

growth/size/body

decreased embryo size ( J:105548 )

• although embryos are smaller than wild-type, they are larger than age-matched homozygous Rb1^tm1Tyj embryos

hematopoietic system

abnormal erythropoiesis ( J:105548 )

• small percentage of erythrocytes exhibit enucleating defects at E17.5, indicating a less severe erythrocyte maturation defect than seen in homozygous Rb1^tm1Tyj mice

embryo

decreased embryo size ( J:105548 )

• although embryos are smaller than wild-type, they are larger than age-matched homozygous Rb1^tm1Tyj embryos

integument

pallor ( J:105548 )

• although embryos are paler than wild-type, they exhibit improved coloration over that seen in homozygous Rb1^tm1Tyj embryos

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (111 available)
Rb1^tm2Brn mutation (3 available); any Rb1 mutation (111 available)
Rbl1^tm1Tyj mutation (1 available); any Rbl1 mutation (60 available)
Tg(Chx10-EGFP/cre,-ALPP)2Clc mutation (1 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (240 available)

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

vision/eye

abnormal eye anterior chamber morphology ( J:120315 )

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

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

abnormal eye posterior chamber morphology ( J:120315 )

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

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

abnormal retina morphology ( J:120315 )

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

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

increased retinoblastoma incidence ( J:120315 )

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

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

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

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

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

neoplasm

increased retinoblastoma incidence ( J:120315 )

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

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

• 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

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

Find Mice

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

vision/eye

increased retinoblastoma incidence ( J:120315 )

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

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

abnormal eye anterior chamber morphology ( J:120315 )

abnormal eye posterior chamber morphology ( J:120315 )

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

neoplasm

increased retinoblastoma incidence ( J:120315 )

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

cellular

abnormal cell proliferation ( J:120315 )

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

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

Find Mice

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

vision/eye

abnormal retina morphology ( J:120315 )

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

• tumor size varies with age and genotype

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

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

increased retinoblastoma incidence ( J:120315 )

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

neoplasm

increased retinoblastoma incidence ( J:120315 )

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

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

Find Mice

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

nervous system

decreased retina photoreceptor cell number ( J:120315 )

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

neoplasm

increased retinoblastoma incidence ( J:120315 )

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

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

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

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

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

vision/eye

abnormal eye posterior chamber morphology ( J:120315 )

abnormal retina morphology ( J:120315 )

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

increased retinoblastoma incidence ( J:120315 )

• 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

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

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

decreased retina photoreceptor cell number ( J:120315 )

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

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 (28 available)
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (111 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 )

increased pituitary gland tumor incidence ( J:47108 )

• only about 62% develop pituitary tumors

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

abnormal thyroid gland morphology ( J:47108 )

• thyroid gland degeneration after 14 months of age

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

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

mortality/aging

prenatal lethality, complete penetrance ( J:47108 )

• no mice of this genotype recovered after birth

Allelic Composition	E2f1^tm1Njd/E2f1^tm1Njd Rb1^tm1Tyj/Rb1^tm1Tyj
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

prenatal lethality, complete penetrance ( J:47108 )

• no double homozygotes recovered after birth

Allelic Composition	Apaf1^tm1Mak/Apaf1^tm1Mak Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0
Genetic Background	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apaf1^tm1Mak mutation (1 available); any Apaf1 mutation (78 available)
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (111 available)
Tg(Rb1)1Blg mutation (0 available)

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

hearing/vestibular/ear

increased cochlear hair cell number ( J:98518 )

• at E18.5, mutant mice display a similar extent of cochlear hair cell overproduction relative to mice that are homozygous for Rb1^tm1Tyj and hemizygous for Tg(Rb1)#Blg

increased vestibular hair cell number ( J:98518 )

• at E18.5, mutant mice display a similar extent of vestibular hair cell overproduction relative to mice that are homozygous for Rb1^tm1Tyj and hemizygous for Tg(Rb1)#Blg

nervous system

increased cochlear hair cell number ( J:98518 )

• at E18.5, mutant mice display a similar extent of cochlear hair cell overproduction relative to mice that are homozygous for Rb1^tm1Tyj and hemizygous for Tg(Rb1)#Blg

increased vestibular hair cell number ( J:98518 )

• at E18.5, mutant mice display a similar extent of vestibular hair cell overproduction relative to mice that are homozygous for Rb1^tm1Tyj and hemizygous for Tg(Rb1)#Blg

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 (111 available)
Trim27^{Gt(XP0484)Wtsi} mutation (0 available); any Trim27 mutation (35 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	Rb1^tm1Tyj/Rb1^tm1Tyj Trim27^{Gt(XP0484)Wtsi}/Trim27^{Gt(XP0484)Wtsi}
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

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

cellular

increased cell proliferation ( J:189317 )

• under a 3T3 protocol, mouse embryonic fibroblasts exhibit increased cell proliferation compared with cells from Trim27^{Gt(XP0484)Wtsi} homozygotes

Allelic Composition	Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0 Trp53^tm1Tyj/Trp53^tm1Tyj
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 (111 available)
Tg(Rb1)1Blg mutation (0 available)
Trp53^tm1Tyj mutation (12 available); any Trp53 mutation (240 available)

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

mortality/aging

postnatal lethality ( J:65679 )

• fewer than expected mice are obtained (no time point of death given)

muscle

abnormal skeletal muscle fiber morphology ( J:65679 )

• skeletal muscle fibers are no different than in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

abnormal muscle physiology ( J:65679 )

• at E18.5, skeletal muscle exhibit an increase in apoptosis compared with Rb1^tm1Tyj/Rb1⁺ Tg(Rb1)1Blg mice

behavior/neurological

hyporesponsive to tactile stimuli ( J:65679 )

hunched posture ( J:65679 )

cellular

polyploidy ( J:65679 )

• as in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

abnormal cell cycle ( J:65679 )

• as in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice, myotubes are unable to exhibit the cell cycle and accumulate enlarged nuclei unlike wild-type myotubes

abnormal retina apoptosis ( J:65679 )

• lens apoptosis is reduced 10-fold compared to in Rb1^tm1Tyj/Rb1^tm1Tyj Trp53^tm1Tyj/Trp53^tm1Tyj Tg(Rb1)1Blg mice

vision/eye

abnormal retina apoptosis ( J:65679 )

• lens apoptosis is reduced 10-fold compared to in Rb1^tm1Tyj/Rb1^tm1Tyj Trp53^tm1Tyj/Trp53^tm1Tyj Tg(Rb1)1Blg mice

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Rb1^tm1Tyj/Rb1^tm1Tyj 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 (63 available)
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (111 available)
Tg(Rb1)1Blg mutation (0 available)

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

skeleton

abnormal deltoid tuberosity morphology ( J:65679 )

• less developed in some mice

absent deltoid tuberosity ( J:65679 )

• in some mice

decreased length of long bones ( J:65679 )

• compared with Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

abnormal scapula morphology ( J:65679 )

• at E16.5, the scapula is brittle and perforated with unclear boundaries between bone and cartilage compared to in heterozygous mice

abnormal sternocostal joint morphology ( J:65679 )

• at E17.5, ribs join the sternim at a 90 degree angle unlike in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

abnormal xiphoid process morphology ( J:65679 )

• at E17.5

abnormal sternum ossification ( J:65679 )

• at E17.5

fragile skeleton ( J:65679 )

muscle

abnormal myogenesis ( J:65679 )

• at E16.5, myotomes undergo nuclei catastrophe and exhibit increased apoptosis compared to in single homozygotes

abnormal skeletal muscle fiber morphology ( J:65679 )

• at E16.5 to E18.5, myotubes exhibit increased nuclear content compared with wild-type myotubes

• at E16.5, myotubes are shorter and more disorganize than in single homozygotes

abnormal muscle physiology ( J:65679 )

• at E16.5, skeletal muscle exhibit an increase in apoptosis compared with Cdkn1a^tm1Tyj/Cdkn1a⁺ Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

behavior/neurological

abnormal posture ( J:65679 )

• more severe than in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

hunched posture ( J:65679 )

• more severe than in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

cardiovascular system

hemorrhage ( J:65679 )

• at E18.5, embryos exhibit patches of hemorrhage unlike wild-type mice

cellular

polyploidy ( J:65679 )

• at E16.5 to E18.5, myotubes exhibit increased nuclear content compared with wild-type myotubes

limbs/digits/tail

abnormal deltoid tuberosity morphology ( J:65679 )

• less developed in some mice

absent deltoid tuberosity ( J:65679 )

• in some mice

Allelic Composition	Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0
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 (111 available)
Tg(Rb1)1Blg mutation (0 available)

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

muscle

abnormal myogenesis ( J:65679 )

• at E18.5, myotubes express reduced levels of late muscle markers unlike wild-type myotubes

abnormal skeletal muscle fiber morphology ( J:65679 )

• at E18.5, myotubes are unable to exhibit the cell cycle, accumulate enlarged polyploidy nuclei, and express reduced levels of late muscle markers unlike wild-type myotubes

behavior/neurological

abnormal posture ( J:65679 )

hunched posture ( J:65679 )

cellular

polyploidy ( J:65679 )

• at E18.5, myotubes are polyploidy unlike wild-type myotubes

abnormal cell cycle ( J:65679 )

• at E18.5, myotubes are unable to exhibit the cell cycle and accumulate enlarged nuclei unlike wild-type myotubes

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

Find Mice

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

skeleton

abnormal xiphoid process morphology ( J:65679 )

• at E17.5

Allelic Composition	E2f1^tm1Meg/E2f1^tm1Meg Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0
Genetic Background	involves: 129S2/SvPas * 129S4/SvJae

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
E2f1^tm1Meg mutation (2 available); any E2f1 mutation (28 available)
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (111 available)
Tg(Rb1)1Blg mutation (0 available)

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

muscle

abnormal skeletal muscle fiber morphology ( J:65679 )

• skeletal muscle fibers are no different than in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

abnormal muscle physiology ( J:65679 )

• at E18.5, skeletal muscle exhibit an increase in apoptosis compared with Rb1^tm1Tyj/Rb1⁺ Tg(Rb1)1Blg mice

behavior/neurological

hyporesponsive to tactile stimuli ( J:65679 )

hunched posture ( J:65679 )

cellular

polyploidy ( J:65679 )

• as in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

abnormal cell cycle ( J:65679 )

• as in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice, myotubes are unable to exhibit the cell cycle and accumulate enlarged nuclei unlike wild-type myotubes

Allelic Composition	Rb1^tm1Tyj/Rb1^tm1Tyj Rbl1^tm1Mru/Rbl1^tm1Mru
Genetic Background	involves: 129S2/SvPas * 129S4/SvJae * BALB/c * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (111 available)
Rbl1^tm1Mru mutation (0 available); any Rbl1 mutation (60 available)

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

nervous system

increased neuronal precursor cell number ( J:92520 )

• mice exhibit increased neuronal precursor numbers due to increased proliferation

• cultured E10 telencephalic neuroepithelia produces more primary neurospheres than cultures from wild-type mice

Allelic Composition	Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0
Genetic Background	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (111 available)
Tg(Rb1)1Blg mutation (0 available)

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

hearing/vestibular/ear

increased cochlear hair cell number ( J:98518 )

• at E18.5, mutant mice display a similar extent of cochlear hair cell overproduction relative to mice that are homozygous for Rb1^tm1Tyj and hemizygous for Tg(Rb1)#Blg

increased vestibular hair cell number ( J:98518 )

• at E18.5, mutant mice display a similar extent of vestibular hair cell overproduction relative to mice that are homozygous for Rb1^tm1Tyj and hemizygous for Tg(Rb1)#Blg

nervous system

increased cochlear hair cell number ( J:98518 )

• at E18.5, mutant mice display a similar extent of cochlear hair cell overproduction relative to mice that are homozygous for Rb1^tm1Tyj and hemizygous for Tg(Rb1)#Blg

increased vestibular hair cell number ( J:98518 )

• at E18.5, mutant mice display a similar extent of vestibular hair cell overproduction relative to mice that are homozygous for Rb1^tm1Tyj and hemizygous for Tg(Rb1)#Blg

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 (111 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 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 parathyroid gland tumor incidence ( J:133299 )

• 50% of mice exhibit parathyroid gland tumors

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

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

increased pancreas tumor incidence ( J:133299 )

• 55% of mice exhibit pancreatic islet tumors

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 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 parathyroid gland tumor incidence ( J:133299 )

• 50% of mice exhibit parathyroid gland tumors

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

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

increased pancreas tumor incidence ( J:133299 )

• 55% of mice exhibit pancreatic islet tumors

Allelic Composition	Kdm5a^tm1.1Kael/Kdm5a⁺ 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 (111 available)

♀	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	Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael 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

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

Find Mice

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

mortality/aging

embryonic lethality, complete penetrance ( J:175625 )

cellular

cellular phenotype ( J:175625 )

N	• embryonic fibroblasts exhibit normal cell proliferation

abnormal cell differentiation ( J:175625 )

• mouse embryonic fibroblasts transfected with a vector expressing Myod1 (MyoD) exhibit reduced differentiate into myocytes unlike similarly treated wild-type cells

• differentiation is enhanced by transfection with the Rb1 variant delta663, which doesn't bind E2F or repress E2F-dependent promoters

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

Find Mice

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

mortality/aging

embryonic lethality, complete penetrance ( J:175625 )

cellular

increased fibroblast proliferation ( J:175625 )

• in mouse embryonic fibroblasts

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 (111 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^tm1Tyj Tg(Rb1)1Blg/0
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 (111 available)
Tg(Rb1)1Blg mutation (0 available)

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

mortality/aging

perinatal lethality, complete penetrance ( J:37145 )

• mutant mice die at birth, indicating partial rescue of the embryonic lethality observed in Rb1^tm1Tyj homozygotes at E13.5-E14.5

muscle

abnormal myogenesis ( J:37145 )

• at E16.5-P0, mutant mice display abnormal myogenesis, with shorter myotubes relative to control mice

• strikingly, when present, mutant myotubes are widely dispersed, and contain enlarged nuclei that are 2-4 times longer than normal

• the number of elongated nuclei increases with time, approaching ~2% and >10% of the myotomal nuclei at E17.5 and E18.5, respectively

• at E17.5, BrdU staining indicates that mutant giant nuclei continue to actively synthesize DNA within myotubes, at a stage when DNA synthesis would have normally ceased

abnormal skeletal muscle morphology ( J:37145 )

• at E16.5-E18.5, TUNEL analysis indicates a significant increase of apoptotic nuclei in mutant skeletal muscles prior to myoblast fusion

• in contrast, no significant increase in apoptosis is noted in mutant cardiac muscles

abnormal skeletal muscle fiber morphology ( J:37145 )

• at E17.5, the myofibrils of mutant limb and tongue muscles are shorter and less abundant, although individual sarcomeric units appear intact

decreased skeletal muscle mass ( J:37145 )

• at birth, mutants exhibit reduced skeletal muscle mass

decreased skeletal muscle fiber density ( J:37145 )

• at E16.5-P0, mutant mice display reduced muscle fiber density in axial, tongue, and limb muscles

behavior/neurological

hunched posture ( J:37145 )

• at E16.5 and P0, mutants display a typical hunchback posture

• however, in contrast to Rb1^tm1Tyj homozygotes, the perichondrium appears normal at E13.5

abnormal stationary movement ( J:37145 )

• at birth, mutants fail to move

skeleton

abnormal spine curvature ( J:37145 )

• at E18.5, mutant mice lack a normal cervical curvature

• however, bones are present and normal in shape

vision/eye

abnormal lens development ( J:37145 )

• at birth, mutant mice exhibit impaired lens development

abnormal lens fiber morphology ( J:37145 )

• at E17.5-P0, mutant mice display significant degeneration of the lens fibers

cellular

polyploidy ( J:98518 )

• in addition to aberrant cochlear and vestibular hair cell proliferation, E18.5 mutant mice exhibit multinucleated and enlarged hair cells in the inner ear sensory epithelia

increased mitotic index ( J:98518 )

• unlike control mice where cells of the organ of Corti and almost all cells of the greater epithelial ridge are postmitotic at E18.5, mutants show ectopic mitoses in the greater epithelial ridge and the region of cochlear inner and outer HCs

• in addition, high numbers of mitotic vestibular hair cells are detected in mutant utricular, saccular, and ampullary sensory epithelia

increased apoptosis ( J:37145 , J:98518 )

• at E16.5-E18.5, TUNEL analysis indicates a significant increase in apoptotic nuclei in mutant axial and tongue muscles (J:37145)

• at E17.5 and E18.5, supernumerary cochlear and vestibular HC production is partially compensated by increased apoptosis in mutant inner ear sensory epithelia (J:98518)

hematopoietic system

abnormal erythropoiesis ( J:37145 )

• in contrast to Rb1^tm1Tyj homozygotes which fail to undergo enucleation of red blood cells, partially rescued mutant mice display only a slight delay in enucleation, with ~2-4% nucleated red blood cells present at E18.5

nervous system

nervous system phenotype ( J:37145 )

N	• at E17.5-P0, mutant mice show a near normal neurogenesis, as shown by normal expression of neuronal markers in brain, trigeminal ganglia, retina, motor neurons, and dorsal root ganglia

increased cochlear hair cell number ( J:98518 )

• at E17.5 and E18.5, mutant mice exhibit excessive proliferation of differentiating cochlear HCs

• at E18.5, the upper basal turn of mutant cochleas shows a 6-fold increase in the numbers of HC nuclei relative to controls

• at birth, mutants display ectopic mitoses in the greater epithelial ridge and the region of cochlear IHCs and OHCs, not present in control mice

• most mitotic cochlear HCs are located near the lumen, while some are found in deeper epithelial layers

• increased mitotic activity and overproduction of cochlear HCs is first evident at E15.5

• at E17.5 and E18.5, supernumerary cochlear HC production is partially compensated by increased apoptosis

increased cochlear inner hair cell number ( J:98518 )

• at E18.5, mutant IHCs are actively cycling, displaying a rounded morphology, typical of dividing cells

increased cochlear outer hair cell number ( J:98518 )

• at E18.5, mutant OHCs are actively cycling, displaying a rounded morphology, typical of dividing cells

abnormal vestibular hair cell morphology ( J:98518 )

• at E17.5 and E18.5, mutants exhibit a hyperplastic vestibular sensory epithelium due to overproduction of HCs

• HCs are abnormally intermixed with supporting cells in the middle layers while the basal part of the epithelium is filled with supernumerary HCs

• some vestibular HCs are mislocated through the basal lamina into the mesenchyme

• a distinct pathology, including multinucleated and enlarged HCs, apoptosis, and infiltration of HCs into the mesenchyme is observed

increased vestibular hair cell number ( J:98518 )

• at E17.5 and E18.5, mutant mice exhibit excessive proliferation of differentiating vestibular HCs

• at E18.5, mutant vestibular HCs are actively cycling, displaying a rounded morphology, typical of dividing cells

• most mitotic vestibular HCs are located at the lumenal surface, but some are found in deeper epithelial levels and in mesenchyme

• increased mitotic activity and overproduction of vestibular HCs is first evident at E14.5

• at E17.5 and E18.5, supernumerary vestibular HC production is partially compensated by increased apoptosis

abnormal vestibular hair cell stereociliary bundle morphology ( J:98518 )

• at birth, mutants display abnormal stereociliary bundle morphologies, particularly in the utricle

• supernumerary vestibular HCs in the deeper epithelial layers and in mesenchyme exhibit disorganized cilia-like protusions and loss of the apicobasal polarity

• however, near-normal stereociliary bundles are also observed, often in ampullae

hearing/vestibular/ear

abnormal organ of Corti morphology ( J:98518 )

• at E17.5 and E18.5, mutant mice exhibit a thickened greater epithelial ridge and a hyperplastic organ of Corti due to excessive hair cell (HC) formation, esp. in the basal half of the cochlea

• however, mutant cochlear HCs exhibit a normal profile of molecules involved in differentiation and maturation

increased cochlear hair cell number ( J:98518 )

• at E17.5 and E18.5, mutant mice exhibit excessive proliferation of differentiating cochlear HCs

• at E18.5, the upper basal turn of mutant cochleas shows a 6-fold increase in the numbers of HC nuclei relative to controls

• at birth, mutants display ectopic mitoses in the greater epithelial ridge and the region of cochlear IHCs and OHCs, not present in control mice

• most mitotic cochlear HCs are located near the lumen, while some are found in deeper epithelial layers

• increased mitotic activity and overproduction of cochlear HCs is first evident at E15.5

• at E17.5 and E18.5, supernumerary cochlear HC production is partially compensated by increased apoptosis

increased cochlear inner hair cell number ( J:98518 )

• at E18.5, mutant IHCs are actively cycling, displaying a rounded morphology, typical of dividing cells

increased cochlear outer hair cell number ( J:98518 )

• at E18.5, mutant OHCs are actively cycling, displaying a rounded morphology, typical of dividing cells

increased organ of Corti supporting cell number ( J:98518 )

• at E17.5 and E18.5, supporting cell numbers are increased, but not to the extent of HC overproduction

• at E18.5, the upper basal turn of mutant cochleas shows a 3-fold increase in the numbers of Deiters' plus pillar cells found below HCs relative to controls

• however, no ectopic mitoses are detected in the mutant supporting cell layer

abnormal vestibular hair cell morphology ( J:98518 )

• at E17.5 and E18.5, mutants exhibit a hyperplastic vestibular sensory epithelium due to overproduction of HCs

• HCs are abnormally intermixed with supporting cells in the middle layers while the basal part of the epithelium is filled with supernumerary HCs

• some vestibular HCs are mislocated through the basal lamina into the mesenchyme

• a distinct pathology, including multinucleated and enlarged HCs, apoptosis, and infiltration of HCs into the mesenchyme is observed

increased vestibular hair cell number ( J:98518 )

• at E17.5 and E18.5, mutant mice exhibit excessive proliferation of differentiating vestibular HCs

• at E18.5, mutant vestibular HCs are actively cycling, displaying a rounded morphology, typical of dividing cells

• most mitotic vestibular HCs are located at the lumenal surface, but some are found in deeper epithelial levels and in mesenchyme

• increased mitotic activity and overproduction of vestibular HCs is first evident at E14.5

• at E17.5 and E18.5, supernumerary vestibular HC production is partially compensated by increased apoptosis

abnormal vestibular hair cell stereociliary bundle morphology ( J:98518 )

• at birth, mutants display abnormal stereociliary bundle morphologies, particularly in the utricle

• supernumerary vestibular HCs in the deeper epithelial layers and in mesenchyme exhibit disorganized cilia-like protusions and loss of the apicobasal polarity

• however, near-normal stereociliary bundles are also observed, often in ampullae

abnormal utricular macula morphology ( J:98518 )

• at birth, the mutant utricular sensory epithelium is hyperplastic due to an excess of HCs, some of which have penetrated into the mesenchyme

Allelic Composition	E2f4^tm1Lees/E2f4⁺ 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 (111 available)

♀	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 (111 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⁺ 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 (111 available)
Trp53^tm1Tyj mutation (12 available); any Trp53 mutation (240 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 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 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 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 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 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

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

♀	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	Rb1^tm1Tyj/Rb1^tm1Tyj Rbl1^tm1Tyj/Rbl1^tm1Tyj
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:34058 )

• at E10.5, 2 out of 10 double mutants are found dead and 2 are noticeably smaller; also, 9 out of 19 double mutants die at E11.5, that is 2 days earlier than mice homozygous for Rb1^tm1Tyj alone

• by E12.5, 7 out of 8 double mutant embryos are either dead or in various stages of resorption

cellular

increased apoptosis ( J:34058 )

• at E11.5, double mutant embryos exhibit a significantly high frequency of pyknotic nuclei (i.e. apoptosis) in the CNS; in contrast, single Rb1^tm1Tyj homozygotes show extensive CNS apoptosis at later stage (E13.5)

• at E12.5 (but not E11.5), a viable double mutant (1 out of 8) exhibits abnormally high levels of apoptosis in the liver and CNS; in contrast, single Rb1^tm1Tyj homozygotes show extensive liver apoptosis at later stage

embryo

abnormal vitelline vasculature morphology ( J:34058 )

• at E11.5, viable double mutant embryos exhibit disorganization of the endothelial linings of yolk sac vessels

decreased embryo size ( J:34058 )

• at E11.5 days, 2 out of 19 double mutant embryos are significantly smaller than control embryos

pale yolk sac ( J:34058 )

• at E11.5, viable double mutant embryos show a significant reduction of erythrocytes in the yolk sac blood vessels

growth/size/body

decreased embryo size ( J:34058 )

• at E11.5 days, 2 out of 19 double mutant embryos are significantly smaller than control embryos

muscle

muscle phenotype ( J:34058 )

N	• at E12.5, double mutant embryos show normal myogenic commitment and differentiation

cardiovascular system

abnormal vitelline vasculature morphology ( J:34058 )

• at E11.5, viable double mutant embryos exhibit disorganization of the endothelial linings of yolk sac vessels

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 (111 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^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 (111 available)
Smarca4^tm1Mag mutation (1 available); any Smarca4 mutation (110 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

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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