p53 mutant mice that display early ageing-associated phenotypes.
Authors: Tyner SD; Venkatachalam S; Choi J; Jones S; Ghebranious N; Igelmann H; Lu X; Soron G; Cooper B; Brayton C; Park SH; Thompson T; Karsenty G; Bradley A; Donehower LA Year: 2002 Journal: Nature Abstract: The p53 tumour suppressor is activated by numerous stressors to induce apoptosis, cell cycle arrest, or senescence. To study the biological effects of altered p53 function, we generated mice with a deletion mutation in the first six exons of the p53 gene that express a truncated RNA capable of encoding a carboxy-terminal p53 fragment. This mutation confers phenotypes consistent with activated p53 rather than inactivated p53. Mutant (p53+/m) mice exhibit enhanced resistance to spontaneous tumours compared with wild-type (p53+/+) littermates. As p53+/m mice age, they display an early onset of phenotypes associated with ageing. These include reduced longevity, osteoporosis, generalized organ atrophy and a diminished stress tolerance. A second line of transgenic mice containing a temperature-sensitive mutant allele of p53 also exhibits early ageing phenotypes. These data suggest that p53 has a role in regulating organismal ageing. Reference
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