Phenotypes Associated with This Genotype

Genotype
MGI:3710321

• Allelic Composition: Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * C57BL/6

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

nervous system

abnormal neuron differentiation ( J:102702 )

• 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

increased medulloblastoma incidence ( J:102702 )

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

neoplasm

increased medulloblastoma incidence ( J:102702 )

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

cellular

abnormal neuron differentiation ( J:102702 )

• 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