A loxP site was inserted upstream of exon 12 and a floxed FRT flanked PGK-neomycin selection cassette was inserted downstream of exon 15 followed by a duplication of exons 12-15. A tyrosine to glutamic acid codon change was incorporated at codon 654 of the duplicated exon 13. Correctly targeted mice were bred to "CAG-flp" mice to remove the selection cassette. Subsequent mating to "CAG-cre" mice substituted the mutated copy of exons 12-15 for the unmodified copy. (J:185942)