Characterization of dystrophin and utrophin diversity in the mouse

Utrophin is a 400 kDa autosomal homolog of dystrophin and a component of th e submembranous cytoskeleton. While multiple dystrophin isoforms have been identified along with alternatively spliced products, to date only two diff erent mRNA species of utrophin have been identified. To determine the degre e of evolutionary conservation between dystrophin and utrophin isoforms, we have compared their expression patterns in adult mice. Northern blot analy sis of multiple adult tissues confirmed that only two major sizes of transc ripts are produced from each gene: 13 and 5.5 kb from utrophin and 14 and 4 .8 kb from dystrophin, However, western blot analysis detected several puta tive short utrophin isoforms that may be homologs of the dystrophin isoform s Dp140, Dp116 and Dp71, We also identified an alternatively spliced utroph in transcript that lacks the equivalent of the alternatively spliced dystro phin exon 71, Finally, we demonstrated that the C-terminal domain of utroph in targeted to neuromuscular junctions in normal mice, but localized to the sarcolemma efficiently only in the absence of dystrophin. Our results prov ide further evidence for a common evolutionary origin of the utrophin and d ystrophin genes.