A single loxP site was inserted 5' to exon 5 and a loxP flanked neomycin and thymidine kinase selection cassette was inserted 3' to exon 5. Exon 5 and the neomycin and thymidine kinase selection cassette were removed in ES cells by Cre mediated recombination prior to the production of chimeric mice, resulting in the null allele.