A floxed neomycin cassette was inserted between exons 2 and 3 and a third loxP site was inserted upstream of exon 2. The neomycin cassette was subsequently removed from properly targeted ES cells by transient transfection with a cre expressing vector. As a result, exon 2 was flanked by loxP sites. The resulting mice were crossed with mice carrying Tg(CMV-cre)1Cgn which caused the germline excision of exon 2. (J:105917)