New mdx mutation disrupts expression of muscle and nonmuscle isoforms of dystrophin


The dystrophin gene encodes several tissue–specific protein isoforms that are generated by alternative splicing and by transcription from at least three separate promoters. We have characterized the mutation in a new strain of mdx mice that results in aberrant splicing of both the 14 and 4.8 kilobase dystrophin mRNAs and disrupts expression of the muscle and brain 427K and nonmuscle 70K isoforms of dystrophin. In contrast, we have determined that expression of the 70K isoform is normal in the original mdx mutant. We have cloned the unique 5′ exon of the murine 4.8 kb mRNA and have analysed the tissue distribution and aberrant splicing of this transcript in the mdx3Cv mutant. This new mdx mutant will provide an improved model system for functional studies of the dystrophin C–terminus in muscle and nonmuscle tissues.

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Cox, G., Phelps, S., Chapman, V. et al. New mdx mutation disrupts expression of muscle and nonmuscle isoforms of dystrophin. Nat Genet 4, 87–93 (1993).

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