The gene was disrupted by replacement of exon 3 and part of intron 3 with a PGK-neo cassette via homologous recombination. The targeted mutation results in deletion of the catalytic domain encoded by exon 3. RT-PCR analysis of RNA from homozygous mutant animals confirmed deletion of exon 3 and revealed a low level exon2-exon4 alternative splice product. The predicted product contains a frameshift mutation resulting in a nonfunctional 125 amino acid protein, of which 98 amino acids are Mbd4-derived. (J:80319)