APO-DYSTROPHINS (DP140 AND DP71) AND DYSTROPHIN SPLICING ISOFORMS IN DEVELOPING BRAIN

PCR studies have shown that exons 71-74 are spliced out in most dystro phin mRNA transcripts in the blain. We have prepared new monoclonal an tibodies against the syntrophin - binding region of dystrophin encoded by exons 73-74 and examined three protein products of the dystrophin gene in brain; the widely distributed Dp71, the recently discovered, b rain-specific Dp140 and dystrophin itself. Exon 73-74 m Abs bound to a ll three proteins in brain and the extent of binding suggests that alt ernatively spliced dystrophins are less prominent at the protein level than predicted by PCR data. Dp140, unlike Dp71, was found to be prese nt at much higher levels in foetal brain than in adult blain. If lack of functional Dp140 is the cause of the cognitive impairment in some D uchenne muscular dystrophy patients, this result suggests that the eff ects may occur early in development, which would reduce the options fo r therapeutic intervention. (C) 1995 Academic Press, Inc.