A 4 kb genomic fragment encompassing exons 11 through 17 was replaced with a neomycin selection cassette inserted by homologous recombination. The deleted region (encoding amino acids 338 through 681) included portions of the X and Y domains, which are putatively essential for enzymatic activity, and a nuclear targeting signal. Western blot analysis showed protein levels to be reduced by approximately 50% in lung tissue obtained from heterozygous mutant mice.