Exon 2, which codes for the signal peptide region, was disrupted by the insertion of a neomycin cassette. To confirm that the gene was correctly targeted, mice were challenged with lipopolysaccharide (LPS) which results in shedding of the Tnfrsf1b extracellular domian in wild-type mice. No soluble Tnfrsf1b was detected in the serum of homozygous mutant animals. (J:21815)