105 bp of exon 3 were deleted to mimic the DM20 isoform and a neomycin resistance cassette was inserted into intron 3 to disrupt splicing of the gene product. Northern blot analysis confirmed the absence of normal transcripts in the brain of homozygous mutant animals. Western blot analysis and silver stained SDS-PAGE gels of myelin samples from homozygous mutants did not detect protein product of either isoform, PLP or DM20. (J:21976)