References
Query Results -- Details
MGI Accession ID: MGI:1351162
J Number: J:59211
Other Accession IDs:
Title: Involvement of p53 in X-ray induced intrachromosomal recombination in mice.
Authors: Aubrecht J; Secretan MB; Bishop AJ; Schiestl RH
Journal: Carcinogenesis
Volume: 20
Issue: 12
Date: 1999 Dec
Year: 1999
Pages: 2229-36
Review Status: Peer Reviewed
Abstract:
The tumor suppressor gene Trp53 (also known as p53) is the most frequently mutated gene in human cancers. p53 is induced in response to DNA damage and effects a G(1) cell cycle arrest. It is believed that p53 plays a key role in maintaining genomic integrity following exposure to DNA-damaging agents. We determined the frequency of spontaneous and DNA damage-induced homologous intrachromosomal recombination in p53-deficient mouse embryos. Homologous intrachromosomal recombination events resulting in deletions at the pink eyed unstable (p(un)) locus result in reversion to the p gene. Reversions occurring in embryonic premelanocytes give rise to black spots on the gray fur of the offspring. Pregnant C57BL/6J p(un)/p(un) p53(+/-) mice were exposed to X-rays (1 Gy) or administered benzoapyrene (BaP; 30 or 150 mg/kg i.p.) 10 days after conception. Frequencies of spontaneous p(un) reversions in p53(-/-) and p53(+/-) animals were not significantly different compared with their wild-type littermates. X-ray treatment increased the recombination frequency in wild-type and p53(+/-), but surprisingly not in p53(-/-) offspring. In contrast, BaP treatment caused a dose-dependent increase in p(un) reversion frequencies in all three genotypes. Western blot analysis of embryos indicated that p53 protein levels increased approximately 3-fold following X-ray treatment, while BaP had no effect on p53 expression. These results are in agreement with the proposal that p53 is involved in the DNA damage response following X-ray exposure and suggest that X-ray-induced double-strand breaks are processed differently in p53(-/-) animals.
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