The targeting construct is designed to insert a codon improved Cre recombinase gene, followed by an FRT-flanked neomycin resistance (neo) cassette, into exon 2 of the gene. Unexpectedly the targeting process resulted in a duplication of all exons of Gcg gene, which spans 9 kb, and extends upstream for at least 17 kb and downstream for at least 7.8 kb, including the neighboring fibroblast activation protein (Fap) gene. Flp-mediated recombination removed the FRT-flanked neo cassette. Mice express Cre in 93-95% of alpha cells and in a negligible amount of beta cells. Cre expression is also seen in intestinal L cells and some neurons in brain. (J:256199)