A targeting vector was constructed so that serines at positions 213-214 were replaced by alanines (codons "CTTCTT" were mutated to "CGCCGC")(SS213-215AA). This mutation occurs in the ATP-binding pocket of the protein and disrupts its kinase activity. A floxed neomycin cassette was also included. F1 mice produced from chimeras were crossed with Cre-transgenic mice to excise the neomycin cassette. Western analysis on macrophages from homozygote null mice indicated the mutant protein was expressed at slightly reduced levels. Abolition of kinase activity of the protein was confirmed by an in vitro assay.