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A region containing a portion of exon 4, encoding the first Kunitz domain, and intron 4 was replaced with a neomycin selection cassette. A truncated peptide, putatively translated from an aberrantly spliced transcript lacking sequence encoding the Kunitz domain, was detected in heterozygotes by Western blot analysis. Densitometric analysis of the blot showed the level of mutant protein in heterozygotes to be approximately 41% of the level of normal protein in wild-type mice. Functional activity was found to be reduced by approximately 46% in heterozygous mutant mice and 100% in homozygotes. (J:41945, J:51137)