A targeting vector was designed to insert a loxP site upstream of exon 3, and an FRT-flanked neomycin resistance (neo) cassette, followed by a second loxP site, downstream of exon 4. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exons 3 through 4 floxed. Subsequent Cre-mediated recombination resulted in the removal of exons 3 and 4 in the germline. (J:229955)