A targeting vector was designed to contain an FRT-flanked neomycin cassette upstream of exon 9, and loxP sites that flank exon 10 which is alternatively spliced only in the Pkm2 isoform. Mutant mice were bred with mice expressing FlpO recombinase (Gt(ROSA)26Sor) to remove the neomycin selection cassette. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have exon 10 deleted in the cre-expressing tissues: pyruvate kinase M2 isoform expression is eliminated, while pyruvate kinase M1 isoform expression is unchanged. (J:205213)