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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adipose Tissue / abnormalities
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Adipose Tissue / metabolism
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Adipose Tissue / pathology
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Aging / genetics*
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Aging, Premature / genetics
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Aging, Premature / metabolism
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Aging, Premature / pathology
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Alleles
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Animals
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Body Weight
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Bone and Bones / cytology
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Bone and Bones / metabolism
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Bone and Bones / pathology
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Cell Transformation, Neoplastic
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Cells, Cultured
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Exons / genetics
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Female
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Genes, p53 / genetics*
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Hair / abnormalities
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Hair / growth & development
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Hair / metabolism
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Longevity / genetics*
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Male
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Mice
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Mice, Transgenic
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Neoplasms / genetics
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Neoplasms / pathology
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Organ Size
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Osteoporosis / genetics
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Phenotype
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Sequence Deletion / genetics*
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Skin / growth & development
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Skin / metabolism
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Skin / pathology
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Tumor Suppressor Protein p53 / chemistry
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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Wound Healing
Substances
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RNA, Messenger
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Tumor Suppressor Protein p53