The site-specific recombinases Cre and Flp can mutate genes in a spatially and temporally restricted manner in mice. Conditional recombination of the tumor suppressor p53 using the Cre-loxP system has led to the development of multiple genetically engineered mouse models of human cancer. However, initiation of tumors with Cre recombinase limits the utilization of Cre to genetically modify other genes in stromal cells. To overcome this limitation, we inserted FRT sites flanking exons 2 through 6 of the endogenous p53 gene in mice to generate a p53FRT allele that can be deleted by Flp recombinase. We show that FlpO-mediated deletion of p53 in mouse embryonic fibroblasts impairs the p53-dependent response to genotoxic stress in vitro. In addition, using FSF-KrasG12D/+; p53FRT/FRT mice, we demonstrate an adenovirus expressing FlpO recombinase can initiate primary lung cancers and sarcomas in mice. p53FRT mice will enable dual recombinase technology to study cancer biology because Cre is available to modify genes specifically in stromal cells to investigate their role in tumor development, progression, and response to therapy.
- Received November 9, 2011.
- Accepted December 21, 2011.
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