| 摘要 |
Ku deficient cells and transgenic animals are described that comprise at least one allele of the XRCC5 gene that has been mutated by targeted disruption. Fibroblasts derived from XRCC5 mutant embryos and mice were found to prematurely age. These cells displayed decreased growth, slow entry into S phase, altered colony side distribution that favored small colonies, short life span and morphology characteristic of terminal differentiation. Mutant cells were also hypersensitive to gamma -radiation. The tissue culture data was at least partly reproduced in vivo because mutant mice grew slower than control littermates. The XRCC5 mutation, designated xrcc5?M1?, was a deletion of nucleotides 701-964 that shifted the reading frame. xrcc5?M1? is expected to be null because the deleted allele produced no detectable transcript and because lymphocyte development and V(D)J recombination was severely disrupted.
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