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

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-dystr...

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Bibliographic Details
Published in:Neuromuscular disorders : NMD 1997-07, Vol.7 (5), p.329-335
Main Authors: Wilton, Stephen D, Dye, Danielle E, Blechynden, Lori M, Laing, Nigel G
Format: Article
Language:English
Subjects:
Alternative processing
Animals
Duchenne muscular dystrophy
Dystrophin
Dystrophin - genetics
Dystrophin - metabolism
Exon skipping
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
Revertant fibres
Sensitivity and Specificity
Transcription, Genetic
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Summary: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.
ISSN:0960-8966
1873-2364
DOI:10.1016/S0960-8966(97)00058-8