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 and Lawrence A. Donehower ()
Additional contact information
Stuart D. Tyner: Cell and Molecular Biology Program
Sundaresan Venkatachalam: Department of Molecular Virology and Microbiology
Jene Choi: Department of Molecular Virology and Microbiology
Stephen Jones: University of Massachusetts Medical Center
Nader Ghebranious: Marshfield Medical Research Foundation
Herbert Igelmann: Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universitat Hamburg
Xiongbin Lu: Department of Molecular Virology and Microbiology
Gabrielle Soron: Department of Molecular Virology and Microbiology
Benjamin Cooper: Department of Molecular Virology and Microbiology
Cory Brayton: Center for Comparative Medicine
Sang Hee Park: Scott Department of Urology
Timothy Thompson: Scott Department of Urology
Gerard Karsenty: Department of Human and Molecular Genetics
Allan Bradley: Department of Human and Molecular Genetics
Lawrence A. Donehower: Department of Molecular Virology and Microbiology

Nature, 2002, vol. 415, issue 6867, 45-53

Abstract: 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.

Date: 2002
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DOI: 10.1038/415045a

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