TY - JOUR
T1 - P53 mutant mice that display early ageing-associated phenotypes
AU - Tyner, Stuart D.
AU - Venkatachalam, Sundaresan
AU - Choi, Jene
AU - Jones, Stephen
AU - Ghebranious, Nader
AU - Igelmann, Herbert
AU - Lu, Xiongbin
AU - Soron, Gabrielle
AU - Cooper, Benjamin
AU - Brayton, Cory
AU - Sang, Hee Park
AU - Thompson, Timothy
AU - Karsenty, Gerard
AU - Bradley, Allan
AU - Donehower, Lawrence A.
N1 - Funding Information:
We thank X.-J. Wang, G. Van Zant, D. Roop, R. Waikel, P. Biggs, M. Patel, S. Wojcik, R. Levasseur, V. Hortenstine, R. Ford, S. Wojcik, C. Pickering, R. Geske and M. Oren for advice and technical assistance. We also thank G. Lozano for luciferase and p53 plasmids. This study was supported by the National Cancer Institute.
PY - 2002/1/3
Y1 - 2002/1/3
N2 - 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.
AB - 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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U2 - 10.1038/415045a
DO - 10.1038/415045a
M3 - Article
C2 - 11780111
AN - SCOPUS:0037011958
SN - 0028-0836
VL - 415
SP - 45
EP - 53
JO - Nature
JF - Nature
IS - 6867
ER -