title: Expression of full-length and truncated dystrophin mini-genes in transgenic mdx mice.
abstract: Duchenne and Becker muscular dystrophy are caused by defects in the dystrophin gene, and are candidates for treatment by gene therapy. We have shown previously that overexpression of a full-length dystrophin cDNA prevents the development of dystrophic symptoms in mdx mice. We show here that this functional correction can be achieved by expressing the full-length muscle isoform at a lower level than is present in control animals. Gene therapy for DMD may necessitate the use of truncated dystrophin mini-genes to accommodate the limited cloning capacity of current-generation viral delivery vectors. We have constructed both murine and human mini-genes deleted for exons 17-48, and have demonstrated that expression of either mini-gene can almost completely prevent the development of dystrophic symptoms in transgenic mdx mice. These results suggest that viral-mediated expression of moderate levels of a truncated dystrophin could be an effective treatment for DMD.
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor 48109-0618, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Phelps
authors.forename: M A
authors.initials: MA
authors.lastname: Hauser
authors.forename: N M
authors.initials: NM
authors.lastname: Cole
authors.forename: J A
authors.initials: JA
authors.lastname: Rafael
authors.forename: R T
authors.initials: RT
authors.lastname: Hinkle
authors.forename: J A
authors.initials: JA
authors.lastname: Faulkner
authors.forename: J S
authors.initials: JS
authors.lastname: Chamberlain
mesh_terms: D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D003964:Diaphragm / Q000378:metabolism; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics / Q000628:therapy; D009137:Muscular Dystrophy, Animal / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D010641:Phenotype; D017384:Sequence Deletion
chemical_list: D018076:DNA, Complementary; D016189:Dystrophin