p53 mutant mice that display early ageing-associated phenotypes

@article{Tyner2002p53MM,
  title={p53 mutant mice that display early ageing-associated phenotypes},
  author={Stuart D. Tyner and Sundaresan Venkatachalam and Jene Choi and Stephen N. Jones and Nader Ghebranious and Herbert Igelmann and Xiongbin Lu and Gabrielle Soron and Benjamin Cooper and Cory F Brayton and Sang Hee Park and Timothy C. Thompson and G{\'e}rard Karsenty and Allan Bradley and Lawrence A. Donehower},
  journal={Nature},
  year={2002},
  volume={415},
  pages={45-53}
}
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… 
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These p53 mutants exhibit increased cancer resistance, yet have a shortened longevity and display a number of early aging‐associated phenotypes, suggesting a role for p53 in the aging process.
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TLDR
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Timed Somatic Deletion of p53 in Mice Reveals Age-Associated Differences in Tumor Progression
TLDR
It is indicated that sustained p53 anti-oncogenic function acts as a final or near final line of defense preventing progression of oncogenically activated cells to malignant tumors.
Complicating the role of p53 in aging
TLDR
It is shown that there are 24 genes deleted in the p53+/m mouse model, complicating the role of p53 in aging and raising the possibility that the phenotypes while resembling ‘premature aging‐like’ symptoms, may not be related to the physiological changes seen during normal aging processes.
'Super p53' mice exhibit enhanced DNA damage response, are tumor resistant and age normally
TLDR
The generation and characterization of mice carrying supernumerary copies of the p53 gene in the form of large genomic transgenes are reported, proving that cancer resistance can be enhanced by a simple genetic modification and in the absence of undesirable effects.
Senescence, aging, and malignant transformation mediated by p53 in mice lacking the Brca1 full-length isoform.
TLDR
In vivo evidence is shown that the absence of the Brca1 full-length isoform causes senescence in mutant embryos and cultured cells as well as aging and tumorigenesis in adult mice, providing the first in vivo evidence that links cellsenescence to aging due to impaired function of Brca2 at the expense of tumorigenisation.
In vivo analysis of p53 tumor suppressor function using genetically engineered mouse models.
TLDR
Studying p53 mouse models has established that both p53-driven cell-cycle arrest and apoptosis responses contribute to tumor suppression and that activation of p53 by oncogenic stress imposes an important barrier to tumorigenesis, suggesting that p53 restoration in human cancer patients may be a promising therapeutic strategy.
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TLDR
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TLDR
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