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Phenotypes Associated with This Genotype
Genotype
MGI:3710321
Allelic
Composition
Cdkn2ctm1Bbd/Cdkn2ctm1Bbd
Trp53tm1Tyj/Trp53tm1Tyj
Genetic
Background
involves: 129S1/Sv * 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2ctm1Bbd mutation (1 available); any Cdkn2c mutation (6 available)
Trp53tm1Tyj mutation (12 available); any Trp53 mutation (155 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• lack of Cdkn2c results in earler evidence of tumor formation, shown by increased neuronal proliferation in cerebellum molecular layer, compared to Cdkn2c-sufficient mice mutants
• in 1-month old mutants injected in the cerebella with BrdU, analysis 9 hours post-injection shows proliferating cells in the superficial molecular layer and the internal granule layer while proliferation has ceased in wild-type cerebella
• there is 3-fold increase in proliferating cells relative to control cerebella
• 50% of double null granule neuronal precursor cells (GNPs) from P12 mice show proliferative capacity compared to wild-type cells (in absence of Shh in culture medium); wild-type cells from P7 mice have mostly exited the cell cycle after 3 days in culture, while many double-null cells continue to incorporate BrdU
• in culture, labeled wild-type cells from P10 and 12 mice that are exposed to Shh show greatly reduced BrdU incorporation compared to double-null cells after 72 hours
• 18/24 (75%) of animals receiving 4 Gy radiation at P5 or 6 develop cerebellar tumors

neoplasm
• 18/24 (75%) of animals receiving 4 Gy radiation at P5 or 6 develop cerebellar tumors

cellular
• lack of Cdkn2c results in earler evidence of tumor formation, shown by increased neuronal proliferation in cerebellum molecular layer, compared to Cdkn2c-sufficient mice mutants
• in 1-month old mutants injected in the cerebella with BrdU, analysis 9 hours post-injection shows proliferating cells in the superficial molecular layer and the internal granule layer while proliferation has ceased in wild-type cerebella
• there is 3-fold increase in proliferating cells relative to control cerebella
• 50% of double null granule neuronal precursor cells (GNPs) from P12 mice show proliferative capacity compared to wild-type cells (in absence of Shh in culture medium); wild-type cells from P7 mice have mostly exited the cell cycle after 3 days in culture, while many double-null cells continue to incorporate BrdU
• in culture, labeled wild-type cells from P10 and 12 mice that are exposed to Shh show greatly reduced BrdU incorporation compared to double-null cells after 72 hours

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
medulloblastoma DOID:0050902 OMIM:155255
J:102702


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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last database update
04/06/2021
MGI 6.16
The Jackson Laboratory