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| p53 mutant mice that display early ageing-associated phenotypes |
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| Author(s): Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu XB, Soron G, Cooper B, Brayton C, Park SH, Thompson T, Karsenty G, Bradley A, Donehower LA |
| Source: NATURE Volume: 415 Issue: 6867 Pages: 45-53 Published: JAN 3 2002 |
| Times Cited: 528 References: 44 |
| 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Donehower, LA (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA |
Addresses:
1. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA
2. Baylor Coll Med, Cell & Mol Biol Program, Houston, TX 77030 USA
3. Baylor Coll Med, Ctr Comparat Med, Houston, TX 77030 USA
4. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA
5. Baylor Coll Med, Dept Human & Mol Genet, Houston, TX 77030 USA
6. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
7. Univ Massachusetts, Med Ctr, Dept Cell Biol, Worcester, MA 01655 USA
8. Marshfield Med Res Fdn, Marshfield, WI 54449 USA
9. Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany
10. Sanger Ctr, Cambridge CB10 1SA, Cambs England |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 507KZ |
| ISSN: 0028-0836 |
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