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A targeting vector was designed to insert a neomycin resistance gene in a sense orientation downstream of the Igamma3 exon, leaving intact all the necessary elements for proper transcription of the gene. Mutants demonstrated a significant impairment In IgG3, but not IgM or IgG2b production. Transcripts of the Igamma3-neo were not detected in RT-PCR, suggesting that the germ line transcription from the promoter was impaired. However, transcript of neo-Cgamma3 was detected, resulting from the TK promoter, and demonstrating that two novel cryptic splice sites were activated, one in the neo and the other in the Igamma3-Cgamma3 intron. (J:107063)