The yeast-derived Flp-frt site-specific DNA recombination system was u
sed to achieve pituitary-specific inactivation of the retinoblastoma (
Rb) tumor suppressor gene. Whereas mice carrying only frt sites in bot
h alleles of Iib remain tumor free, tumorigenesis ensues when the Flp
recombinase is expressed. The rate of tumorigenesis in these mice depe
nds both on the expression level of the Flp recombinase and on the pre
sence of frt sites in one or both Rb alleles. This permitted a more ac
curate definition of the consecutive steps in pituitary tumorigenesis.
Our study illustrates the potential of this approach for studying spo
radic cancer in a defined mouse model.