Phenotypes Associated with This Genotype

Genotype
MGI:3702289

• Allelic Composition: Hus1^tm1Led/Hus1^tm2Rsw
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

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

cellular

abnormal chromosome morphology ( J:118898 )

• cultured mouse embryonic fibroblasts (MEFs) show an increased percentage of chromosomal aberrations compared to all other genotypes; by the third passage, 48% of metaphase spreads show at least one abnormality, while 32% have multiple abnormalities

• in vivo, mice show an elevated level of chromosomal instability compared to controls

abnormal cell physiology ( J:118898 )

• cells show reduced viability in response to treatment with amphidicolin; cells are 5-fold more sensitive to the replication inhibitor than Hus1^tm1Led /+ cells

abnormal cell cycle checkpoint function ( J:118898 )

• after BPDE treatment, DNA synthesis is maintained at 79.4% of untreated controls cultures, while Hus1^tm1Led/+ cultures show a reduction of DNA synthesis to 61.9% of control; this indicates that the S-phase damage checkpoint inhibiting DNA synthesis in response to genome damage is decreased in effectiveness

decreased cell proliferation ( J:118898 )

• MEFs from mutants show severely limited growth capacity compared to wild-type MEFs

chromosome breakage ( J:118898 )

• MEFs show a greater accumulation of double strand breaks after amphidicolin treatment than control cells with increased levels of chromatid interchanges

induced chromosome breakage ( J:118898 )

• MEFs show significantly increased sensitivity to DNA lesion-inducing agent BPDE; only 18.8% of cells remain viable 72 hours after treatment compared to 46% of heterozygous cells

oxidative stress ( J:118898 )

• treatment of cells with an antioxidant (NAC) almost completely suppresses the premature senescence