Developmental and tissue-specific regulation of mouse dystrophin: the embryonic isoform in muscular dystrophy.

Dystrophin, the protein product of the Duchenne muscular dystrophy locus, is encoded by a 14 kb transcript of over 65 exons. A point mutation in the homologous mouse gene causes muscular dystrophy in mdx mice. We have examined the developmental regulation of transcription of this gene in skeletal mouse muscle and also the tissue specificity of the transcript in muscle and brain, by using the polymerase chain reaction to amplify overlapping segments of dystrophin mRNA spanning the entire coding sequence and 5'-untranslated region. We have characterised a specific embryonic transcript that would encode dystrophin with a different C-terminus and have shown that this persists from the earliest stages to the adult in mdx skeletal muscle. The brain transcript shows striking sequence homology to rat and human, being highly conserved at the 5'-untranslated region and is present in both wild-type and mdx mice.