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p53 mutant mice that display early ageing-associated phenotypes.
Authors:Stuart D Tyner  Sundaresan Venkatachalam  Jene Choi  Stephen Jones  Nader Ghebranious  Herbert Igelmann  Xiongbin Lu  Gabrielle Soron  Benjamin Cooper  Cory Brayton  Sang Hee Park  Timothy Thompson  Gerard Karsenty  Allan Bradley  Lawrence A Donehower
Affiliation:Cell and Molecular Biology Program, Baylor College of Medicine, Houston, TX 77030, USA.
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.
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