| First Author | Torgovnick A | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 4 | Pages | 1027-1039.e6 |
| PubMed ID | 30355482 | Mgi Jnum | J:266858 |
| Mgi Id | MGI:6257991 | Doi | 10.1016/j.celrep.2018.09.079 |
| Citation | Torgovnick A, et al. (2018) The Cdkn1a(SUPER) Mouse as a Tool to Study p53-Mediated Tumor Suppression. Cell Rep 25(4):1027-1039.e6 |
| abstractText | Cdkn1a, which encodes p21, functions as a major route for p53-mediated cell-cycle arrest. However, the consequence of Cdkn1a gene dosage on tumor suppression has not been systematically investigated. Here, we employed BAC transgenesis to generate a Cdkn1a(SUPER) mouse, which harbors an additional Cdkn1a allele within its natural genomic context. We show that these mice display enhanced cell-cycle arrest and reduced apoptosis in response to genotoxic stress. Furthermore, using a chemically induced skin cancer model and an autochthonous Kras-driven lung adenocarcinoma model, we show that Cdkn1a(SUPER) mice display a cancer protection phenotype that is indistinguishable from that observed in Tp53(SUPER) animals. Moreover, we demonstrate that Tp53 and Cdkn1a cooperate in mediating cancer resistance, using a chemically induced fibrosarcoma model. Overall, our Cdkn1a(SUPER) allele enabled us to assess the contribution of Cdkn1a to Tp53-mediated tumor suppression. |
