Insertion of a loxP-flanked neomycin-thymidine kinase expression cassette replaced the mouse DNA-binding domain (exons 4-9) with the corresponding homologous segment of the normal human gene, leaving transcription under control of the endogenous promoter. Cre-mediated recombination in ES cells excised the neo-tk sequences. cDNA sequencing studies determined that transcripts from spleen of homozygous mutant mice carried the human sequence for exons 4-9, and that the gene is correctly spliced and transcribed. (J:68918)