| First Author | Christophorou MA | Year | 2005 |
| Journal | Nat Genet | Volume | 37 |
| Issue | 7 | Pages | 718-26 |
| PubMed ID | 15924142 | Mgi Jnum | J:99305 |
| Mgi Id | MGI:3581952 | Doi | 10.1038/ng1572 |
| Citation | Christophorou MA, et al. (2005) Temporal dissection of p53 function in vitro and in vivo. Nat Genet 37(7):718-26 |
| abstractText | 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. |
