The targeting construct inserted loxP sites flanked wild-type exon 4 with a 3' neomycin resistance cassette followed by a mutant exon 4 with nucleotide substitutions (TCA to GAC) that results in the amino acid substitution of serine with aspartic acid at position 193 (S193D). Cre-mediated recombination removed the wild-type exon 4 and the selection cassette. (J:311936)