title: Direct retroviral-mediated transfer of a dystrophin minigene into mdx mouse muscle in vivo.
abstract: At the cellular level, the primary pathology in Duchenne muscular dystrophy (DMD) is caused by deficiency of the sarcolemmal-associated protein, dystrophin, in the striated musculature. Here we describe the somatic transfer and long-term expression of a human dystrophin minigene corresponding to a mild Becker muscular dystrophy (BMD) phenotype in skeletal muscle tissues of the dystrophin-deficient mdx mouse by direct retroviral transduction. Following a single intramuscular injection of recombinant retrovirus, sarcolemmal expression of dystrophin was observed in an average of approximately 6% of myofibres in treated tibialis anterior muscles and was associated with activated reappearance of at least one component (43kD) of the dystrophin-glycoprotein membrane complex (DGC). Furthermore, expression of recombinant dystrophin was observed in muscle tissues up to 9 months after treatment and a significant enhancement of retrovirus-mediated myofibre transduction was obtained in mdx muscle undergoing experimentally-induced regeneration. The results clearly demonstrate that retroviral transduction of activated satellite cells in regenerating skeletal muscle is a feasible route for direct and stable dystrophin gene transfer into muscle tissues in vivo.
authors.affiliation: Department of Experimental Pathology, UMDS, Guy's Hospital, London, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Dunckley
authors.forename: D J
authors.initials: DJ
authors.lastname: Wells
authors.forename: F S
authors.initials: FS
authors.lastname: Walsh
authors.forename: G
authors.initials: G
authors.lastname: Dickson
mesh_terms: D000818:Animals; D016189:Dystrophin / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D005813:Genes, Synthetic; D005816:Genetic Complementation Test; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007273:Injections, Intramuscular; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D008817:Mice, Mutant Strains / Q000235:genetics*; D009136:Muscular Dystrophies / Q000235:genetics*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000628:therapy*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D012508:Sarcolemma / Q000378:metabolism; D014162:Transfection
chemical_list: D016189:Dystrophin; D011994:Recombinant Proteins