Phenotypes associated with this allele

• Allele Symbol: Tmub1^{tm1(KOMP)Vlcg}
• Allele Name: targeted mutation 1, Velocigene
• Allele ID: MGI:4842927
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tmub1^tm1(KOMP)Vlcg/Tmub1^tm1(KOMP)Vlcg	involves: C57BL/6 * C57BL/6NTac	MGI:6471883

Genotype
MGI:6471883

hm1

• Allelic Composition: Tmub1^{tm1(KOMP)Vlcg}/Tmub1^{tm1(KOMP)Vlcg}
• Genetic Background: involves: C57BL/6 * C57BL/6NTac

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

mortality/aging

preweaning lethality, incomplete penetrance ( J:284575 )

• following crosses between homozygous males and heterozygous females, homozygous mutant mice are obtained at a slightly reduced Mendelian frequency at ~P21 (weaning)

cellular

abnormal cell physiology ( J:284575 )

• cycloheximide-treated MEFs show a significantly lower p53 half-life than similarly treated wild-type MEFs, indicating increased p53 degradation

decreased sensitivity to induced cell death ( J:284575 )

• mice show significant resistance to etoposide-induced apoptosis in the thymus, spleen and testis, as shown by cleaved caspase-3 immunofluorescence and TUNEL staining

• in vitro, mouse embryo fibroblasts (MEFs) show significantly reduced apoptosis levels in response to etoposide or camptothecin treatment relative to wild-type MEFs

• however, thymocytes show normal levels of apoptosis induced by dexamethasone, a p53-independent apoptogenic stimulus

abnormal apoptosis ( J:284575 )

• mice do not undergo p53-driven mitochondrial apoptosis

abnormal mitochondrial physiology ( J:284575 )

• etoposide-treated mice fail to show an accumulation of p53 mitochondrial protein levels in thymus, spleen and testis, unlike similarly treated wild-type mice

• in vitro, etoposide-treated thymocytes and splenocytes show a lower mitochondrial accumulation of p53 and higher cell viability relative to similarly treated wild-type cells

• etoposide-treated MEFs stained with vital dye JC-1 show a reduction in p53-dependent mitochondrial membrane potential loss relative to similarly treated wild-type MEFs

• however, mitochondria isolated from MEFs show normal cytochrome c release after addition of recombinant p53, indicating normal mitochondrial outer membrane permeability

reproductive system

reduced fertility ( J:284575 )

• homozygous mice show a reduced ability to produce offspring