The sequence encoding the final three C-terminal residues (arginine-glycine-threonine) that are necessary for interaction with Src kinase were targeted for removal. Targeting constructs also contained several silent mutations to introduce new HpaI and NdeI restriction sites and a floxed neomycin-resistance cassette between exons 14 and 15. Mice carrying the mutation were crossed with cre transgenic mice to remove the neomycin selection cassette. Extracellular protein expression levels on homozygous platelets was only 59% of wild-type levels, which was similar to that found on heterozygous null platelets.