Molecular Info®

Molecular Info® Copy Right © 2001 Institute of Molecular Development LLC

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, SANG HEE PARK, TIMOTHY THOMPSON, GERARD KARSENTY, ALLAN BRADLEY & LAWRENCE A. DONEHOWER The Nature, January 2002, 415: 45 - 53. 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.