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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Rb1tm1Tyj
targeted mutation 1, Tyler Jacks
MGI:1857242
Summary 42 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Rb1tm1Tyj/Rb1tm1Tyj involves: 129S2/SvPas MGI:2166359
hm2
Rb1tm1Tyj/Rb1tm1Tyj involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N MGI:5296666
hm3
Rb1tm1Tyj/Rb1tm1Tyj involves: 129S2/SvPas * C57BL/6 MGI:3582488
ht4
Rb1tm1Tyj/Rb1+ involves: 129S2/SvPas MGI:5614091
ht5
Rb1tm1Tyj/Rb1+ involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N MGI:5296667
ht6
Rb1tm1Tyj/Rb1+ involves: 129S2/SvPas * C57BL/6 MGI:3582548
ht7
Rb1tm1Tyj/Rb1+ involves: 129S2/SvPas * C57BL/6J MGI:3839771
ht8
Rb1tm1Tyj/Rb1tm2Tyj chimera involves: 129S2/SvPas * C57BL/6 MGI:3843184
ht9
Rb1tm1Dwg/Rb1tm1Tyj involves: 129/Sv * 129S2/SvPas * C57BL/6 MGI:3618362
cn10
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1tm1Tyj
Trp53tm1Brn/Trp53tm1Brn
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL MGI:3710238
cn11
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1tm1Tyj
Trp53tm1Brn/Trp53tm1Tyj
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL MGI:3710239
cn12
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1+
Trp53tm1Brn/Trp53tm1Brn
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL MGI:3710240
cn13
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1+
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL MGI:3710241
cx14
E2f1tm1Njd/E2f1tm1Njd
Rb1tm1Tyj/Rb1+
either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6) MGI:3840353
cx15
E2f1tm1Njd/E2f1+
Rb1tm1Tyj/Rb1+
either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6) MGI:3840352
cx16
E2f1tm1Njd/E2f1+
Rb1tm1Tyj/Rb1tm1Tyj
either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6) MGI:3840351
cx17
E2f1tm1Njd/E2f1tm1Njd
Rb1tm1Tyj/Rb1tm1Tyj
either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6) MGI:3840350
cx18
Apaf1tm1Mak/Apaf1tm1Mak
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 MGI:3699923
cx19
Rb1tm1Tyj/Rb1+
Trim27Gt(XP0484)Wtsi/Trim27Gt(XP0484)Wtsi
involves: 129P2/OlaHsd * C57BL/6 MGI:5446920
cx20
Rb1tm1Tyj/Rb1tm1Tyj
Trim27Gt(XP0484)Wtsi/Trim27Gt(XP0484)Wtsi
involves: 129P2/OlaHsd * C57BL/6 MGI:5446919
cx21
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
Trp53tm1Tyj/Trp53tm1Tyj
involves: 129S2/SvPas MGI:4420470
cx22
Cdkn1atm1Tyj/Cdkn1atm1Tyj
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
involves: 129S2/SvPas MGI:4420466
cx23
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
involves: 129S2/SvPas MGI:4420468
cx24
Cdkn1atm1Tyj/Cdkn1atm1Tyj
Rb1tm1Tyj/Rb1+
Tg(Rb1)1Blg/0
involves: 129S2/SvPas MGI:4420467
cx25
E2f1tm1Meg/E2f1tm1Meg
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
involves: 129S2/SvPas * 129S4/SvJae MGI:4420469
cx26
Rb1tm1Tyj/Rb1tm1Tyj
Rbl1tm1Mru/Rbl1tm1Mru
involves: 129S2/SvPas * 129S4/SvJae * BALB/c * C57BL/6 MGI:4353990
cx27
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
involves: 129S2/SvPas * 129S4/SvJae * C57BL/6 MGI:3699919
cx28
Men1tm1.1Ctre/Men1+
Rb1tm1Tyj/Rb1+
involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J * FVB/N MGI:3839773
cx29
Kdm5atm1.1Kael/Kdm5a+
Rb1tm1Tyj/Rb1+
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N MGI:5296663
cx30
Kdm5atm1.1Kael/Kdm5atm1.1Kael
Rb1tm1Tyj/Rb1+
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N MGI:5296664
cx31
Kdm5atm1.1Kael/Kdm5atm1.1Kael
Rb1tm1Tyj/Rb1tm1Tyj
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N MGI:5296668
cx32
Kdm5atm1.1Kael/Kdm5a+
Rb1tm1Tyj/Rb1tm1Tyj
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N MGI:5296665
cx33
Rb1tm1Tyj/Rb1+
Tg(Th-MYCN)41Waw/0
involves: 129S2/SvPas * BALB/c * C57BL/6J MGI:5009553
cx34
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
involves: 129S2/SvPas * C57BL/6 MGI:3699732
cx35
E2f4tm1Lees/E2f4+
Rb1tm1Tyj/Rb1+
involves: 129S2/SvPas * C57BL/6 MGI:3582523
cx36
Rb1tm1Tyj/Rb1+
Rbl1tm1Tyj/Rbl1tm1Tyj
involves: 129S2/SvPas * C57BL/6 MGI:3582581
cx37
Rb1tm1Tyj/Rb1+
Trp53tm1Tyj/Trp53+
involves: 129S2/SvPas * C57BL/6 MGI:3582787
cx38
E2f4tm1Lees/E2f4tm1Lees
Rb1tm1Tyj/Rb1+
involves: 129S2/SvPas * C57BL/6 MGI:3582517
cx39
Rb1tm1Tyj/Rb1tm1Tyj
Rbl1tm1Tyj/Rbl1tm1Tyj
involves: 129S2/SvPas * C57BL/6 MGI:3582586
cx40
Rb1tm1Tyj/Rb1+
Rbl1tm1Tyj/Rbl1+
involves: 129S2/SvPas * C57BL/6 MGI:3582618
cx41
Rb1tm1Tyj/Rb1+
Tg(S100b-v-erbB)4496Waw/0
involves: 129S2/SvPas * C57BL/6J * DBA/2J * FVB/N MGI:3822322
cx42
Rb1tm1Tyj/Rb1+
Smarca4tm1Mag/Smarca4+
involves: 129S/Sv * 129S2/SvPas * C57BL/6J * CD-1 MGI:5763442


Genotype
MGI:2166359
hm1
Allelic
Composition
Rb1tm1Tyj/Rb1tm1Tyj
Genetic
Background
involves: 129S2/SvPas
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• live homozygotes are rarely recovered at E15.5 and never at E16.5

hematopoietic system
• 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
• significant decrease in the percentage of enucleated erythrocytes, indicating defective erythrocyte maturation
• at E13.5, peripheral blood smears contain predominantly nucleated erythrocytes

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

nervous system
• at E13.5, apoptosis is increased in the brain, dorsal root ganglia, and trigeminal ganglia
• at E13.5, proliferation is increased in the brain, dorsal root ganglia, and trigeminal ganglia
• detect ectopic mitosis and apoptosis in the intermediate zones of the fourth ventricle
• detect ectopic mitosis and apoptosis in the intermediate zones of the third ventricle
• detect ectopic mitosis and apoptosis in the trigeminal ganglia
• detect ectopic mitosis and apoptosis in the dorsal root ganglia

vision/eye
• apoptosis is detected in the lens fiber compartment that is not seen in wild-type
• at E13.5, ectopic proliferating cells are seen in the interior of the lens and increased apoptosis is seen
• detect ectopic mitoses in the lens fiber compartment that is not seen in wild-type
• lens fiber cells are disorganized

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

cellular
• MEFs exhibit an increase in the fraction of cells in the S and G2/M phases of the cell cycle
• MEFs fail to efficiently trigger G1/S cell cycle arrest in response to DNA damage
• apoptosis is detected in the lens fiber compartment that is not seen in wild-type
• at E13.5, apoptosis is increased in the brain, dorsal root ganglia, and trigeminal ganglia
• 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
• at E13.5, proliferation is increased in the brain, dorsal root ganglia, and trigeminal ganglia
• MEFs cultured at confluence exhibit an increase in cell proliferation compared to wild-type MEFs

embryo
• normal labyrinth architecture is disrupted
• the porous appearance of the labyrinth layer is absent
• 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

immune system
• 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




Genotype
MGI:5296666
hm2
Allelic
Composition
Rb1tm1Tyj/Rb1tm1Tyj
Genetic
Background
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

cellular
• 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




Genotype
MGI:3582488
hm3
Allelic
Composition
Rb1tm1Tyj/Rb1tm1Tyj
Genetic
Background
involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• homozygous mutant embryos die between E14.5 and E15.5 (J:2511)

hematopoietic system
• at E13.5, homozygotes are severely pale relative to wild-type embryos
• 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%)
• at E13.5, homozygotes display impaired definitive erythropoiesis and fail to produce sufficient numbers of mature erythrocytes, resulting in hypoxia and eventually death
• 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
• 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)
• at E13.5, homozygotes display a slight reduction in liver size

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

nervous system
N
• normal numbers of primary neurospheres are produced from cultured E10 telencephalic neuroepithelia
• 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
N
• at E13.5, homozygotes display normal retinal development

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

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

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

integument
• at E13.5, edema results in damage of the dermis and underlying mesenchyme
• however, most non-hematopoietic tissues remain unaffected until death (~E14.5)




Genotype
MGI:5614091
ht4
Allelic
Composition
Rb1tm1Tyj/Rb1+
Genetic
Background
involves: 129S2/SvPas
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• mice develop pituitary gland tumors with a mean survival of 400 days

endocrine/exocrine glands
• mice develop pituitary gland tumors with a mean survival of 400 days

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

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




Genotype
MGI:5296667
ht5
Allelic
Composition
Rb1tm1Tyj/Rb1+
Genetic
Background
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• in 9 of 10 mice; 5 of 5 with intermediate lobe origins

endocrine/exocrine glands
• in 9 of 10 mice; 5 of 5 with intermediate lobe origins

mortality/aging
• median survival is 47 weeks

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




Genotype
MGI:3582548
ht6
Allelic
Composition
Rb1tm1Tyj/Rb1+
Genetic
Background
involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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)

endocrine/exocrine glands
• 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)
• 23/27 heterozygotes show c-cell thyroid tumors

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

neoplasm
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
• 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)
• 23/27 heterozygotes show c-cell thyroid tumors

growth/size/body
• at 8-10 months of age, a number of heterozygotes display severe wasting




Genotype
MGI:3839771
ht7
Allelic
Composition
Rb1tm1Tyj/Rb1+
Genetic
Background
involves: 129S2/SvPas * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• mice exhibit tumors of the pituitary anterior lobe (42%)
• however, no parathyroid adenomas are observed
• all mice exhibit tumors of the pituitary intermediate lobe
• all mice exhibit metastic thyroid C-cell carcinomas

respiratory system

nervous system
• mice exhibit tumors of the pituitary anterior lobe (42%)
• however, no parathyroid adenomas are observed
• all mice exhibit tumors of the pituitary intermediate lobe

mortality/aging
• median lifespan is 372 days compared to 546 days for Men1tm1.1Ctre heterozygotes

neoplasm
• mice exhibit tumors of the pituitary anterior lobe (42%)
• however, no parathyroid adenomas are observed
• all mice exhibit tumors of the pituitary intermediate lobe
• all mice exhibit metastic thyroid C-cell carcinomas
• 60% of mice exhibit lung metastasis




Genotype
MGI:3843184
ht8
Allelic
Composition
Rb1tm1Tyj/Rb1tm2Tyj
Genetic
Background
chimera involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Rb1tm2Tyj mutation (0 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• severe adenocarcenomas by 3-4 months of age in chimeric mice
• derived from the intermediate lobe

growth/size/body
• display severe wasting and become moribund by 3-4 months

neoplasm
• severe adenocarcenomas by 3-4 months of age in chimeric mice
• derived from the intermediate lobe
• hyperchromatic cells are found in the adrenal medulla of chimeric mice indicating neoplastic lesions

nervous system
N
• examined in chimeric mice
• severe adenocarcenomas by 3-4 months of age in chimeric mice
• derived from the intermediate lobe
• cells with enlarged nuclei
• displaced Purkinje cells

liver/biliary system
• abnormally large nuclei in chimeric mice

vision/eye
N
• examined in chimeric mice
• no retinoblastomas
• normal retinal architecture
• 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




Genotype
MGI:3618362
ht9
Allelic
Composition
Rb1tm1Dwg/Rb1tm1Tyj
Genetic
Background
involves: 129/Sv * 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Dwg mutation (0 available); any Rb1 mutation (78 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• survive as long as homozygous Rb1tm1Dwg mice, with 2 of 18 dead at E15.5 and 4 of 7 dead at E17.5

growth/size/body
• although embryos are smaller than wild-type, they are larger than age-matched homozygous Rb1tm1Tyj embryos

hematopoietic system
• small percentage of erythrocytes exhibit enucleating defects at E17.5, indicating a less severe erythrocyte maturation defect than seen in homozygous Rb1tm1Tyj mice

embryo
• although embryos are smaller than wild-type, they are larger than age-matched homozygous Rb1tm1Tyj embryos

integument
• although embryos are paler than wild-type, they exhibit improved coloration over that seen in homozygous Rb1tm1Tyj embryos




Genotype
MGI:3710238
cn10
Allelic
Composition
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1tm1Tyj
Trp53tm1Brn/Trp53tm1Brn
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
Genetic
Background
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (78 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (12 available)
Tg(Chx10-EGFP/cre,-ALPP)2Clc mutation (1 available)
Trp53tm1Brn mutation (17 available); any Trp53 mutation (191 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants; tumor size varies with age and genotype
• an early-stage tumor displayed a pronounced vitreal protrusion in one animal, and contained structures resembling neuronal processes like those in the plexiform layer of the normal retina
• in tumors, proteins usually found in amacrine/horizontal cells, including Gad65, Snap25, Calbindin, vGlut-1, E-cadherin, N-cadherin, synapsin, and Syntaxin-1 are expressed; these cells are considered to be differentiated
• cells positive for amacrine/horizontal cell markers (1.7-3.6 x 106 cells/tumor) are much more numerous than number of amacrine/horizontal cells in a normal retina
• regions of tumors negative for amacrine/horizontal markers contain more densely packed nuclei
• tumor cells that invade the anterior eye chamber beneath the cornea are densely packed stage II cells surrounded by sparse regions of plexus with no synaptic densities or vesiclesin in the plexus or rosettes of these cells
• tumor cells have abundant mitochondria and mitotic figures; some rosettes have a central plexus made up of large, undifferentiated processes, with other rosettes having a central plexus containing neurons and synapses
• areas of the plexus within the posterior chamber are composed of neuron-like processes having synaptic structures similar to horizontal/amacrine cells; this is seen in smaller areas of plexus in tumors
• processes are usually smaller in diameter (<0.5 um) but large ones of 1-3 um are observed occasionally; variety of synaptic arrangements occur and all types can be found in contacts among processes, while ribbon synapses are seen only in areas near photoreceptor cell bodies
• significant disruptions in retinal morphology are observed by P12 to 13
• in diseased eyes, retina blastoma cells rupture the inner limiting membrane (ILM), particularly by the apex of vitreal protrusions that may be present; at these points, tumor cell bodies and associated vasculature can be seen

neoplasm
• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants; tumor size varies with age and genotype
• an early-stage tumor displayed a pronounced vitreal protrusion in one animal, and contained structures resembling neuronal processes like those in the plexiform layer of the normal retina
• in tumors, proteins usually found in amacrine/horizontal cells, including Gad65, Snap25, Calbindin, vGlut-1, E-cadherin, N-cadherin, synapsin, and Syntaxin-1 are expressed; these cells are considered to be differentiated
• cells positive for amacrine/horizontal cell markers (1.7-3.6 x 106 cells/tumor) are much more numerous than number of amacrine/horizontal cells in a normal retina
• regions of tumors negative for amacrine/horizontal markers contain more densely packed nuclei




Genotype
MGI:3710239
cn11
Allelic
Composition
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1tm1Tyj
Trp53tm1Brn/Trp53tm1Tyj
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
Genetic
Background
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (78 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (12 available)
Tg(Chx10-EGFP/cre,-ALPP)2Clc mutation (1 available)
Trp53tm1Brn mutation (17 available); any Trp53 mutation (191 available)
Trp53tm1Tyj mutation (12 available); any Trp53 mutation (191 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites
• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber
• tumor cells that invade the anterior eye chamber beneath the cornea are densely packed stage II cells surrounded by sparse regions of plexus with no synaptic densities or vesiclesin in the plexus or rosettes of these cells
• tumor cells have abundant mitochondria and mitotic figures; some rosettes have a central plexus made up of large, undifferentiated processes, with other rosettes having a central plexus containing neurons and synapses
• areas of the plexus within the posterior chamber are composed of neuron-like processes having synaptic structures similar to horizontal/amacrine cells; this is seen in extensive plexus areas of tumors

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

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




Genotype
MGI:3710240
cn12
Allelic
Composition
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1+
Trp53tm1Brn/Trp53tm1Brn
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
Genetic
Background
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (78 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (12 available)
Tg(Chx10-EGFP/cre,-ALPP)2Clc mutation (1 available)
Trp53tm1Brn mutation (17 available); any Trp53 mutation (191 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• significant disruptions in retinal morphology are observed by P12 to 13
• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants, but onset is delayed compared to that observed in Rbl1 homozygous compound mutants
• tumor size varies with age and genotype
• mice show rapid filling of the vitreal cavity with densely packed tumor cells and rosettes; in the tumors, there is an overabundance of stage II retinoblastoma cells
• near outer surface of retina near tumor origin site, there are regions of plexus with synaptic densities and synaptic vesicles, indistinguishable from the Rb1;Rbl1 mutants that are wild-type for Trp53

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




Genotype
MGI:3710241
cn13
Allelic
Composition
Rb1tm1Tyj/Rb1tm2Brn
Rbl1tm1Tyj/Rbl1+
Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
Genetic
Background
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Rb1tm2Brn mutation (3 available); any Rb1 mutation (78 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (12 available)
Tg(Chx10-EGFP/cre,-ALPP)2Clc mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• mice with retinoblastoma tumors are characterized by pronounced loss of photoreceptor cells

neoplasm
• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites
• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber
• tumors show appearance of unique populations of undifferentiated tumor-like cells, and extensive formation of plexiform regions
• in a large tumor that filled much of the vitreal space contained two cell types: some cells are stage I retinoblastoma cells with pale, round nuclei resembling differentiated neurons and always associated with a plexus or tightly-packed stage II retinoblastoma cells with irregular nuclei with little or no plexus associated with individual cells
• rosettes in retinoblastomas are usually composed of stage I cells with a central plexus, but are adjacent to clusters of stage II cells
• plexus regions of tumors show mitotic figures and apoptotic cells; plexus regions also contained synaptic densities and associated synaptic vesicles

vision/eye
• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites
• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber
• tumors show appearance of unique populations of undifferentiated tumor-like cells, and extensive formation of plexiform regions
• in a large tumor that filled much of the vitreal space contained two cell types: some cells are stage I retinoblastoma cells with pale, round nuclei resembling differentiated neurons and always associated with a plexus or tightly-packed stage II retinoblastoma cells with irregular nuclei with little or no plexus associated with individual cells
• rosettes in retinoblastomas are usually composed of stage I cells with a central plexus, but are adjacent to clusters of stage II cells
• plexus regions of tumors show mitotic figures and apoptotic cells; plexus regions also contained synaptic densities and associated synaptic vesicles
• areas of the plexus within the posterior chamber are composed of neuron-like processes having synaptic structures similar to horizontal/amacrine cells; this is seen in smaller areas of plexus in tumors
• processes are usually smaller in diameter (<0.5 um) but large ones of 1-3 um are observed occasionally; variety of synaptic arrangements occur and all types can be found in contacts among processes, while ribbon synapses are seen only in areas near photoreceptor cell bodies
• significant disruptions in retinal morphology are observed by P12 to 13
• mice with retinoblastoma tumors are characterized by pronounced loss of photoreceptor cells




Genotype
MGI:3840353
cx14
Allelic
Composition
E2f1tm1Njd/E2f1tm1Njd
Rb1tm1Tyj/Rb1+
Genetic
Background
either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
E2f1tm1Njd mutation (1 available); any E2f1 mutation (6 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• only about 62% develop pituitary tumors
• pituitary tumors are smaller than Rb1tm1Tyj heterozygotes but histologically indistinguishable

mortality/aging
• increased survival relative to Rb1tm1Tyj heterozygotes, 15.2 months on a 129 background and up to 17 months on a mixed background

neoplasm
• only about 62% develop pituitary tumors
• pituitary tumors are smaller than Rb1tm1Tyj heterozygotes but histologically indistinguishable
• fewer thyroid C-cell adenomas than in Rb1tm1Tyj heterozygotes

endocrine/exocrine glands
• thyroid gland degeneration after 14 months of age
• only about 62% develop pituitary tumors
• pituitary tumors are smaller than Rb1tm1Tyj heterozygotes but histologically indistinguishable
• fewer thyroid C-cell adenomas than in Rb1tm1Tyj heterozygotes

reproductive system

cardiovascular system




Genotype
MGI:3840352
cx15
Allelic
Composition
E2f1tm1Njd/E2f1+
Rb1tm1Tyj/Rb1+
Genetic
Background
either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
E2f1tm1Njd mutation (1 available); any E2f1 mutation (6 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• fewer thyroid C-cell adenomas than in Rb1tm1Tyj heterozygotes

mortality/aging
• increased survival relative to Rb1tm1Tyj heterozygotes, 11.6 months on a 129 background and up to 12.6 months on a mixed background

neoplasm
• develop grossly detectable pituitary tumors
• fewer thyroid C-cell adenomas than in Rb1tm1Tyj heterozygotes




Genotype
MGI:3840351
cx16
Allelic
Composition
E2f1tm1Njd/E2f1+
Rb1tm1Tyj/Rb1tm1Tyj
Genetic
Background
either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
E2f1tm1Njd mutation (1 available); any E2f1 mutation (6 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• no mice of this genotype recovered after birth




Genotype
MGI:3840350
cx17
Allelic
Composition
E2f1tm1Njd/E2f1tm1Njd
Rb1tm1Tyj/Rb1tm1Tyj
Genetic
Background
either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
E2f1tm1Njd mutation (1 available); any E2f1 mutation (6 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• no double homozygotes recovered after birth




Genotype
MGI:3699923
cx18
Allelic
Composition
Apaf1tm1Mak/Apaf1tm1Mak
Rb1tm1Tyj/Rb1tm1Tyj
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:
Apaf1tm1Mak mutation (1 available); any Apaf1 mutation (8 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Tg(Rb1)1Blg mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hearing/vestibular/ear
• at E18.5, mutant mice display a similar extent of cochlear hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg
• at E18.5, mutant mice display a similar extent of vestibular hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg

nervous system
• at E18.5, mutant mice display a similar extent of cochlear hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg
• at E18.5, mutant mice display a similar extent of vestibular hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg




Genotype
MGI:5446920
cx19
Allelic
Composition
Rb1tm1Tyj/Rb1+
Trim27Gt(XP0484)Wtsi/Trim27Gt(XP0484)Wtsi
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Trim27Gt(XP0484)Wtsi mutation (0 available); any Trim27 mutation (28 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• as in Rb1tm1Tyj heterozygotes

endocrine/exocrine glands
• as in Rb1tm1Tyj heterozygotes
• as in Rb1tm1Tyj heterozygotes

neoplasm
• as in Rb1tm1Tyj heterozygotes
• as in Rb1tm1Tyj heterozygotes
• as in Rb1tm1Tyj heterozygotes




Genotype
MGI:5446919
cx20
Allelic
Composition
Rb1tm1Tyj/Rb1tm1Tyj
Trim27Gt(XP0484)Wtsi/Trim27Gt(XP0484)Wtsi
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Trim27Gt(XP0484)Wtsi mutation (0 available); any Trim27 mutation (28 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• under a 3T3 protocol, mouse embryonic fibroblasts exhibit increased cell proliferation compared with cells from Trim27Gt(XP0484)Wtsi homozygotes




Genotype
MGI:4420470
cx21
Allelic
Composition
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
Trp53tm1Tyj/Trp53tm1Tyj
Genetic
Background
involves: 129S2/SvPas
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Tg(Rb1)1Blg mutation (0 available)
Trp53tm1Tyj mutation (12 available); any Trp53 mutation (191 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• fewer than expected mice are obtained (no time point of death given)

muscle
• skeletal muscle fibers are no different than in Rb1tm1Tyj/Rb1tm1Tyj Tg(Rb1)1Blg mice
• at E18.5, skeletal muscle exhibit an increase in apoptosis compared with Rb1tm1Tyj/Rb1+ Tg(Rb1)1Blg mice

behavior/neurological

cellular
• as in Rb1tm1Tyj/Rb1tm1Tyj Tg(Rb1)1Blg mice
• as in Rb1tm1Tyj/Rb1tm1Tyj Tg(Rb1)1Blg mice, myotubes are unable to exhibit the cell cycle and accumulate enlarged nuclei unlike wild-type myotubes
• lens apoptosis is reduced 10-fold compared to in Rb1tm1Tyj/Rb1tm1Tyj Trp53tm1Tyj/Trp53tm1Tyj Tg(Rb1)1Blg mice

vision/eye
• lens apoptosis is reduced 10-fold compared to in Rb1tm1Tyj/Rb1tm1Tyj Trp53tm1Tyj/Trp53tm1Tyj Tg(Rb1)1Blg mice

integument




Genotype
MGI:4420466
cx22
Allelic
Composition
Cdkn1atm1Tyj/Cdkn1atm1Tyj
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
Genetic
Background
involves: 129S2/SvPas
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Tyj mutation (3 available); any Cdkn1a mutation (53 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Tg(Rb1)1Blg mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• less developed in some mice
• in some mice
• compared with Rb1tm1Tyj/Rb1tm1Tyj Tg(Rb1)1Blg mice
• at E16.5, the scapula is brittle and perforated with unclear boundaries between bone and cartilage compared to in heterozygous mice
• at E17.5, ribs join the sternim at a 90 degree angle unlike in Rb1tm1Tyj/Rb1tm1Tyj Tg(Rb1)1Blg mice

muscle
• at E16.5, myotomes undergo nuclei catastrophe and exhibit increased apoptosis compared to in single homozygotes
• 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
• at E16.5, skeletal muscle exhibit an increase in apoptosis compared with Cdkn1atm1Tyj/Cdkn1a+ Rb1tm1Tyj/Rb1tm1Tyj Tg(Rb1)1Blg mice

behavior/neurological
• more severe than in Rb1tm1Tyj/Rb1tm1Tyj Tg(Rb1)1Blg mice
• more severe than in Rb1tm1Tyj/Rb1tm1Tyj Tg(Rb1)1Blg mice

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

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

limbs/digits/tail
• less developed in some mice
• in some mice




Genotype
MGI:4420468
cx23
Allelic
Composition
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
Genetic
Background
involves: 129S2/SvPas
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Tg(Rb1)1Blg mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
muscle
• at E18.5, myotubes express reduced levels of late muscle markers unlike wild-type myotubes
• 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

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




Genotype
MGI:4420467
cx24
Allelic
Composition
Cdkn1atm1Tyj/Cdkn1atm1Tyj
Rb1tm1Tyj/Rb1+
Tg(Rb1)1Blg/0
Genetic
Background
involves: 129S2/SvPas
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Tyj mutation (3 available); any Cdkn1a mutation (53 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Tg(Rb1)1Blg mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton




Genotype
MGI:4420469
cx25
Allelic
Composition
E2f1tm1Meg/E2f1tm1Meg
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
Genetic
Background
involves: 129S2/SvPas * 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
E2f1tm1Meg mutation (2 available); any E2f1 mutation (6 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Tg(Rb1)1Blg mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
muscle
• skeletal muscle fibers are no different than in Rb1tm1Tyj/Rb1tm1Tyj Tg(Rb1)1Blg mice
• at E18.5, skeletal muscle exhibit an increase in apoptosis compared with Rb1tm1Tyj/Rb1+ Tg(Rb1)1Blg mice

behavior/neurological

cellular
• as in Rb1tm1Tyj/Rb1tm1Tyj Tg(Rb1)1Blg mice
• as in Rb1tm1Tyj/Rb1tm1Tyj Tg(Rb1)1Blg mice, myotubes are unable to exhibit the cell cycle and accumulate enlarged nuclei unlike wild-type myotubes

integument




Genotype
MGI:4353990
cx26
Allelic
Composition
Rb1tm1Tyj/Rb1tm1Tyj
Rbl1tm1Mru/Rbl1tm1Mru
Genetic
Background
involves: 129S2/SvPas * 129S4/SvJae * BALB/c * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Rbl1tm1Mru mutation (0 available); any Rbl1 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• mice exhibit increased neuronal precursor numbers due to increased proliferation
• cultured E10 telencephalic neuroepithelia produces more primary neurospheres than cultures from wild-type mice




Genotype
MGI:3699919
cx27
Allelic
Composition
Rb1tm1Tyj/Rb1tm1Tyj
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:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Tg(Rb1)1Blg mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hearing/vestibular/ear
• at E18.5, mutant mice display a similar extent of cochlear hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg
• at E18.5, mutant mice display a similar extent of vestibular hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg

nervous system
• at E18.5, mutant mice display a similar extent of cochlear hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg
• at E18.5, mutant mice display a similar extent of vestibular hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg




Genotype
MGI:3839773
cx28
Allelic
Composition
Men1tm1.1Ctre/Men1+
Rb1tm1Tyj/Rb1+
Genetic
Background
involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Men1tm1.1Ctre mutation (2 available); any Men1 mutation (14 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• mice exhibit pituitary anterior lobe tumors (40% of mice)
• pituitary intermediate lobe tumors (96% of mice)

endocrine/exocrine glands
• adrenal cortical tumor (10% of mice)
• 55% of mice exhibit pancreatic islet tumors
• 50% of mice exhibit parathyroid gland tumors
• mice exhibit pituitary anterior lobe tumors (40% of mice)
• pituitary intermediate lobe tumors (96% of mice)
• mice exhibit thyroid C-cell carcinomas (96%)

mortality/aging
• median lifespan is 402 days compared to 546 days for Men1tm1.1Ctre heterozygotes

neoplasm
• adrenal cortical tumor (10% of mice)
• 55% of mice exhibit pancreatic islet tumors
• 50% of mice exhibit parathyroid gland tumors
• mice exhibit pituitary anterior lobe tumors (40% of mice)
• pituitary intermediate lobe tumors (96% of mice)
• mice exhibit thyroid C-cell carcinomas (96%)
• metastasis in the lungs (70% of mice)




Genotype
MGI:5296663
cx29
Allelic
Composition
Kdm5atm1.1Kael/Kdm5a+
Rb1tm1Tyj/Rb1+
Genetic
Background
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kdm5atm1.1Kael mutation (1 available); any Kdm5a mutation (9 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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

endocrine/exocrine glands
• 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

neoplasm
• 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




Genotype
MGI:5296664
cx30
Allelic
Composition
Kdm5atm1.1Kael/Kdm5atm1.1Kael
Rb1tm1Tyj/Rb1+
Genetic
Background
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kdm5atm1.1Kael mutation (1 available); any Kdm5a mutation (9 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• in 8 of 10 mice; 3 of 4 with intermediate lobe origins and 1 in 4 anterior lobe origins

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

mortality/aging
• median survival is 72 weeks

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




Genotype
MGI:5296668
cx31
Allelic
Composition
Kdm5atm1.1Kael/Kdm5atm1.1Kael
Rb1tm1Tyj/Rb1tm1Tyj
Genetic
Background
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kdm5atm1.1Kael mutation (1 available); any Kdm5a mutation (9 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

cellular
N
• embryonic fibroblasts exhibit normal cell proliferation
• 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




Genotype
MGI:5296665
cx32
Allelic
Composition
Kdm5atm1.1Kael/Kdm5a+
Rb1tm1Tyj/Rb1tm1Tyj
Genetic
Background
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kdm5atm1.1Kael mutation (1 available); any Kdm5a mutation (9 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

cellular
• in mouse embryonic fibroblasts




Genotype
MGI:5009553
cx33
Allelic
Composition
Rb1tm1Tyj/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:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Tg(Th-MYCN)41Waw mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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

neoplasm
• 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

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




Genotype
MGI:3699732
cx34
Allelic
Composition
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
Genetic
Background
involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Tg(Rb1)1Blg mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mutant mice die at birth, indicating partial rescue of the embryonic lethality observed in Rb1tm1Tyj homozygotes at E13.5-E14.5

muscle
• 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
• 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
• at E17.5, the myofibrils of mutant limb and tongue muscles are shorter and less abundant, although individual sarcomeric units appear intact
• at birth, mutants exhibit reduced skeletal muscle mass
• at E16.5-P0, mutant mice display reduced muscle fiber density in axial, tongue, and limb muscles

behavior/neurological
• at E16.5 and P0, mutants display a typical hunchback posture
• however, in contrast to Rb1tm1Tyj homozygotes, the perichondrium appears normal at E13.5
• at birth, mutants fail to move

skeleton
• at E18.5, mutant mice lack a normal cervical curvature
• however, bones are present and normal in shape

vision/eye
• at birth, mutant mice exhibit impaired lens development
• at E17.5-P0, mutant mice display significant degeneration of the lens fibers

cellular
• 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
• 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
• 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
• in contrast to Rb1tm1Tyj 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
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
• 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
• at E18.5, mutant IHCs are actively cycling, displaying a rounded morphology, typical of dividing cells
• at E18.5, mutant OHCs are actively cycling, displaying a rounded morphology, typical of dividing cells
• 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
• 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
• 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
• 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
• 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
• at E18.5, mutant IHCs are actively cycling, displaying a rounded morphology, typical of dividing cells
• at E18.5, mutant OHCs are actively cycling, displaying a rounded morphology, typical of dividing cells
• however, no ectopic mitoses are detected in the mutant supporting cell layer
• 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
• 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
• 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
• 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
• at birth, the mutant utricular sensory epithelium is hyperplastic due to an excess of HCs, some of which have penetrated into the mesenchyme




Genotype
MGI:3582523
cx35
Allelic
Composition
E2f4tm1Lees/E2f4+
Rb1tm1Tyj/Rb1+
Genetic
Background
involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
E2f4tm1Lees mutation (1 available); any E2f4 mutation (14 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• developed pituitary tumors that were comparable to those arising in single heterozygous mutant Rb1 mice with respect to both incidence and size

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

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

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




Genotype
MGI:3582581
cx36
Allelic
Composition
Rb1tm1Tyj/Rb1+
Rbl1tm1Tyj/Rbl1tm1Tyj
Genetic
Background
involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• similar to Rb1tm1Tyj heterozygotes, all surviving mutant mice develop large pituitary adenocarcinomas of the intermediate lobe

mortality/aging
• females displaying vaginal atresia accumulate fluid in the uterus and die between 4 and 6 months of age
• similar to Rb1tm1Tyj heterozygotes, any surviving mutant mice eventually die of pituitary tumors after 12 months
• 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

growth/size/body
• mutant pups become runted several days after birth
• 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
• 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
• females displaying vaginal atresia have a distended abdomen as a result of fluid accumulation in the uterus

neoplasm
• similar to Rb1tm1Tyj heterozygotes, all surviving mutant mice develop large pituitary adenocarcinomas of the intermediate lobe

reproductive system
• females displaying vaginal atresia have a distended perineum as a result of fluid accumulation in the uterus
• ~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
• 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
• as early as 4 days after birth, mutant newborns exhibit mild, yet significant, disruptions of the retinal photoreceptor layer

nervous system
• similar to Rb1tm1Tyj heterozygotes, all surviving mutant mice develop large pituitary adenocarcinomas of the intermediate lobe
• as early as 4 days after birth, mutant newborns exhibit mild, yet significant, disruptions of the retinal photoreceptor layer

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




Genotype
MGI:3582787
cx37
Allelic
Composition
Rb1tm1Tyj/Rb1+
Trp53tm1Tyj/Trp53+
Genetic
Background
involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Trp53tm1Tyj mutation (12 available); any Trp53 mutation (191 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe

muscle
• one of 7 individual double heterozygotes analyzed displayed a leiomyosarcoma

endocrine/exocrine glands
• 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
• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe
• ~75% of double heterozygous mice develop medullary thyroid tumors

mortality/aging
• the mean age of survival of double heterozygotes is slightly reduced relative to mice heterozygous for Rb1tm1Tyj alone (9 months vs 11 months)

neoplasm
• 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
• 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
• 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
• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe
• ~75% of double heterozygous mice develop medullary thyroid tumors
• 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 Trp53tm1Tyj heterozygotes
• notably, the wild-type alleles of both Rb1 and Trp53 were lost in these anaplastic sarcomas
• one of 7 individual double heterozygotes analyzed displayed a leiomyosarcoma

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




Genotype
MGI:3582517
cx38
Allelic
Composition
E2f4tm1Lees/E2f4tm1Lees
Rb1tm1Tyj/Rb1+
Genetic
Background
involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
E2f4tm1Lees mutation (1 available); any E2f4 mutation (14 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
• 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
• 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




Genotype
MGI:3582586
cx39
Allelic
Composition
Rb1tm1Tyj/Rb1tm1Tyj
Rbl1tm1Tyj/Rbl1tm1Tyj
Genetic
Background
involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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 Rb1tm1Tyj alone
• by E12.5, 7 out of 8 double mutant embryos are either dead or in various stages of resorption

cellular
• at E11.5, double mutant embryos exhibit a significantly high frequency of pyknotic nuclei (i.e. apoptosis) in the CNS; in contrast, single Rb1tm1Tyj 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 Rb1tm1Tyj homozygotes show extensive liver apoptosis at later stage

embryo
• at E11.5, viable double mutant embryos exhibit disorganization of the endothelial linings of yolk sac vessels
• at E11.5 days, 2 out of 19 double mutant embryos are significantly smaller than control embryos
• at E11.5, viable double mutant embryos show a significant reduction of erythrocytes in the yolk sac blood vessels

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

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

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




Genotype
MGI:3582618
cx40
Allelic
Composition
Rb1tm1Tyj/Rb1+
Rbl1tm1Tyj/Rbl1+
Genetic
Background
involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Rbl1tm1Tyj mutation (1 available); any Rbl1 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• double heterozygotes develop large pituitary tumors of the intermediate lobe that are comparable to those arising in single Rb1tm1Tyj 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
• double heterozygotes develop large pituitary tumors of the intermediate lobe that are comparable to those arising in single Rb1tm1Tyj 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

mortality/aging
• similar to Rb1tm1Tyj heterozygotes, mice heterozygous for both Rb1tm1Tyj and Rbl1tm1Tyj die from tumors in the intermediate lobe of the pituitary gland at ~12 months of age

neoplasm
• double heterozygotes develop large pituitary tumors of the intermediate lobe that are comparable to those arising in single Rb1tm1Tyj 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




Genotype
MGI:3822322
cx41
Allelic
Composition
Rb1tm1Tyj/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:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Tg(S100b-v-erbB)4496Waw mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• mice develop gliomas in the same pattern and with the same pathology as in Tg(S100b-v-erbB)4496Waw mice

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




Genotype
MGI:5763442
cx42
Allelic
Composition
Rb1tm1Tyj/Rb1+
Smarca4tm1Mag/Smarca4+
Genetic
Background
involves: 129S/Sv * 129S2/SvPas * C57BL/6J * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (78 available)
Smarca4tm1Mag mutation (1 available); any Smarca4 mutation (83 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• mice develop pituitary tumors with 100% penetrance and median latency period of 12-13 months

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

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

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





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last database update
02/16/2021
MGI 6.16
The Jackson Laboratory