title: Expression of dog microdystrophin in mouse and dog muscles by gene therapy.
abstract: Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin. Several previous studies demonstrated the feasibility of delivering microdystrophin complementary DNA (cDNA) into mouse and normal nonhuman primate muscles by ex vivo gene therapy. However, these animal models do not reproduce completely the human DMD phenotype, while the dystrophic dog model does. To progress toward the use of the best animal model of DMD, a dog microdystrophin was transduced into human and dystrophic dog muscle precursor cells (MPCs) with a lentivirus before their transplantation into mouse muscles. One month following MPC transplantation, myofibers expressing the dog microdystrophin were observed. We also used another approach to introduce this transgene into myofibers, i.e., the electrotransfer of a plasmid coding for the dog microdystrophin. The plasmid was injected into mouse and dog muscles, and brief electric pulses were applied in the region of injection. Two weeks later, the transgene was detected in both animals. Therefore, ex vivo gene therapy and electrotransfer are two possible methods to introduce a truncated version of dystrophin into myofibers of animal models and eventually into myofibers of DMD patients.
authors.affiliation: Unité de Recherche en Génétique Humaine, Faculté de Médecine, Centre de recherche du CHUL, CHUQ, Université Laval, Québec, Quebec, Canada.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pichavant
authors.forename: Pierre
authors.initials: P
authors.lastname: Chapdelaine
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Cerri
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Dominique
authors.forename: Simon P
authors.initials: SP
authors.lastname: Quenneville
authors.forename: Daniel
authors.initials: D
authors.lastname: Skuk
authors.forename: Joe N
authors.initials: JN
authors.lastname: Kornegay
authors.forename: João Cs
authors.initials: JC
authors.lastname: Bizario
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Tremblay
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004285:Dogs; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy; D010957:Plasmids / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D016189:Dystrophin