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-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.
Wilton
S D
SD
Australian Neuromuscular Research Institute, Nedlands, Australia.
Dye
D E
DE
Blechynden
L M
LM
Laing
N G
NG
D000818:Animals; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D009154:Mutation; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic
D016189:Dystrophin