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A construct was created in which a floxed neomycin cassette was inserted immediately upstream of the exons encoding the catalytic tyrosine kinase domain. An additional loxP site was inserted at the 3' terminal of this region. Transient transfection of ES cells with plasmids expressing cre-recombinase generated an allele which lacked both the inserted neomycin gene and the catalytic domain encoding exon. Northern blot analyses using various probes showed that a truncated transcript lacking the catalytic domain was produced in homozygous mutant mice. Additionally, absence of the tyrosine kinase domain encoding region was confirmed by RT-PCR. (J:47538)