P53 mutant mice that display early ageing-associated phenotypes

Stuart D. Tyner, Sundaresan Venkatachalam, Jene Choi, Stephen Jones, Nader Ghebranious, Herbert Igelmann, Xiongbin Lu, Gabrielle Soron, Benjamin Cooper, Cory Brayton, Hee Park Sang, Timothy Thompson, Gerard Karsenty, Allan Bradley, Lawrence A. Donehower

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)45-53
Number of pages9
JournalNature
Volume415
Issue number6867
DOIs
StatePublished - Jan 3 2002
Externally publishedYes

ASJC Scopus subject areas

  • General

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