The targeting construct included exons 2-4 of the gene and a neomycin cassette flanked by loxP sequences. Clones were transfected with a Cre plasmid. ES cell lines showing a deletion of exons 2-4 and the neomycin cassette were selected for microinjection. The mutation was confirmed by PCR, Southern blot and in situ hybridization. (J:92100)