A gene trap cassette inserted into intron 1 of the gene. The gene trap cassette includes a splice adaptor at the 5 end with neomycin selection and poly(A) termination signals followed by another ES cell-only promotor that expresses the first exon of the Brutons tyrosine kinase gene with multiple termination codons to prevent expression of downstream fusion transcripts. Immunoblot analysis confirmed the absence of protein expression in isolated mouse embryonic fibroblasts (MEFs) and tissues from homozygous mutant mice. (J:246421)