CECAD Microsite

Christian Reinhardt Lab

Alessandro Torgovnick's paper on the Cdkn1aSUPER Mouse as a Tool to Study p53-Mediated Tumor Suppression is published.


Torgovnick et al. create a mouse model, carrying a third copy of Cdkn1a (p21), which shows enhanced cell-cycle arrest capacity and protection against DNA damage-induced apoptosis. The Cdkn1aSUPER animals display delayed epithelial regeneration and a robust cancer resistance phenotype, highlighting the importance of p21 in p53-dependent tumor suppression.

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 notbeen systematically investigated. Here, Alessandro Torgovnick and colleges employed BAC transgenesis to generate a Cdkn1aSUPER mouse, which harbors an additional Cdkn1a allele within its natural genomic context. 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 Krasdriven lung adenocarcinoma model, Torgovnick et al. showed that Cdkn1aSUPER mice display a cancer protection phenotype that is indistinguishable from that observed in Tp53SUPER animals. Moreover, Torgovnick et al. demonstrated that Tp53 and Cdkn1a cooperate in mediating cancer resistance, using a chemically induced fibrosarcoma model. Overall, the Cdkn1aSUPER allele enabled to assess the contribution of Cdkn1a to Tp53-mediated tumor suppression.