title: p53 mutant mice that display early ageing-associated phenotypes.
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.
authors.affiliation: Cell and Molecular Biology Program, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Tyner
authors.forename: Sundaresan
authors.initials: S
authors.lastname: Venkatachalam
authors.forename: Jene
authors.initials: J
authors.lastname: Choi
authors.forename: Stephen
authors.initials: S
authors.lastname: Jones
authors.forename: Nader
authors.initials: N
authors.lastname: Ghebranious
authors.forename: Herbert
authors.initials: H
authors.lastname: Igelmann
authors.forename: Xiongbin
authors.initials: X
authors.lastname: Lu
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Soron
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cooper
authors.forename: Cory
authors.initials: C
authors.lastname: Brayton
authors.forename: Sang Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Timothy
authors.initials: T
authors.lastname: Thompson
authors.forename: Gerard
authors.initials: G
authors.lastname: Karsenty
authors.forename: Allan
authors.initials: A
authors.lastname: Bradley
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Donehower
mesh_terms: D000273:Adipose Tissue / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D000375:Aging / Q000235:genetics*; D019588:Aging, Premature / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000483:Alleles; D000818:Animals; D001835:Body Weight; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005091:Exons / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006197:Hair / Q000002:abnormalities / Q000254:growth & development / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D009929:Organ Size; D010024:Osteoporosis / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*; D012867:Skin / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53