A targeting vector containing an ACN self-excising loxP-flanked neomycin cassette and a diptheria toxin (DTA) gene is used to replace the serine residue at position 216 of exon 3 with an alanine residue. The left homology arm included all of exons 2, 3, and 4 (including the S216A substitution codon), while the right homology arm contained part of intron 4. (J:300412)