The Cdkn1aSUPER Mouse as a Tool to Study p53-Mediated Tumor Suppression

Alessandro Torgovnick*, Jan Michel Heger, Vasiliki Liaki, Jörg Isensee, Anna Schmitt, Gero Knittel, Arina Riabinska, Filippo Beleggia, Lucie Laurien, Uschi Leeser, Christian Jüngst, Florian Siedek, Wenzel Vogel, Niklas Klümper, Hendrik Nolte, Maike Wittersheim, Lars Tharun, Roberta Castiglione, Marcus Krüger, Astrid SchaussSven Perner, Manolis Pasparakis, Reinhard Büttner, Thorsten Persigehl, Tim Hucho, Grit Sophie Herter-Sprie, Björn Schumacher, Hans Christian Reinhardt

*Corresponding author for this work
2 Citations (Scopus)


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 Cdkn1aSUPER 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 Cdkn1aSUPER mice display a cancer protection phenotype that is indistinguishable from that observed in Tp53SUPER animals. Moreover, we demonstrate that Tp53 and Cdkn1a cooperate in mediating cancer resistance, using a chemically induced fibrosarcoma model. Overall, our Cdkn1aSUPER allele enabled us to assess the contribution of Cdkn1a to Tp53-mediated tumor suppression. 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.

Original languageEnglish
JournalCell Reports
Issue number4
Pages (from-to)1027-1039.e6
Publication statusPublished - 23.10.2018


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