Revertant fibres: a possible genetic therapy for Duchenne muscular dystrophy?

Neuromuscul Disord. 1997 Jul;7(5):329-35. doi: 10.1016/s0960-8966(97)00058-8.

Abstract

The mdx mouse, an animal model used to study Duchenne muscular dystrophy (DMD), has a nonsense mutation in exon 23 of the dystrophin gene which should result in a truncated protein that cannot be correctly localized at the sarcolemma of the muscle fibres. Immunohistochemical staining with anti-dystrophin antibodies had shown that while most of the muscle tissue was dystrophin-negative, a small percentage of muscle fibres were clearly dystrophin-positive and had somehow by-passed the primary nonsense mutation. A nested PCR-based examination of dystrophin gene transcripts around the mdx mutation revealed several alternatively processed transcripts, of which four mRNA species skipped the mutation in exon 23, were in-frame and could be translated into a shorter, but still functional dystrophin protein. Specific tests for these transcripts demonstrated these were also present in normal adult and embryonic mouse muscle tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dystrophin / genetics
  • Dystrophin / metabolism*
  • Exons
  • Genetic Therapy*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx / genetics
  • Muscle Fibers, Skeletal / metabolism*
  • Muscular Dystrophy, Animal / genetics
  • Muscular Dystrophy, Animal / metabolism*
  • Muscular Dystrophy, Animal / therapy*
  • Mutation
  • Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Transcription, Genetic

Substances

  • Dystrophin