Induced mitotic recombination of p53 in vivo.

Genetic mosaics produced by FLP/FRT induced mitotic recombination have been widely used in Drosophila to study gene function in development. Recently, the Cre/loxP system has been applied to induce mitotic recombination in mouse embryonic stem cells and in many adult mouse tissues. We have used this strategy to generate a previously undescribed p53 mouse model in which expression of a ubiquitously expressed recombinase in a heterozygous p53 knockout animal produces mitotic recombinant clones homozygous for the p53 mutation. The induction of loss of heterozygosity in a few cells in an otherwise normal tissue mimics genetic aspects of tumorigenesis more closely than existing models and has revealed the possible cell autonomous nature of Wnt3. Our results suggest that inducible mitotic recombination can be used for clonal analysis of mutants in the mouse.