Temporal dissection of p53 function in vitro and in vivo - PubMed (original) (raw)
doi: 10.1038/ng1572. Epub 2005 May 29.
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- PMID: 15924142
- DOI: 10.1038/ng1572
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Temporal dissection of p53 function in vitro and in vivo
Maria A Christophorou et al. Nat Genet. 2005 Jul.
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Abstract
To investigate the functions of the p53 tumor suppressor, we created a new knock-in gene replacement mouse model in which the endogenous Trp53 gene is substituted by one encoding p53ER(TAM), a p53 fusion protein whose function is completely dependent on ectopic provision of 4-hydroxytamoxifen. We show here that both tissues in vivo and cells in vitro derived from such mice can be rapidly toggled between wild-type and p53 knockout states. Using this rapid perturbation model, we define the kinetics, dependence, persistence and reversibility of p53-mediated responses to DNA damage in tissues in vivo and to activation of the Ras oncoprotein and stress in vitro. This is the first example to our knowledge of a new class of genetic model that allows the specific, rapid and reversible perturbation of the function of a single endogenous gene in vivo.
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