title: Myoblast transplantations lead to the expression of the laminin alpha 2 chain in normal and dystrophic (dy/dy) mouse muscles.
abstract: Laminin-2 is part of the basement membrane of the skeletal muscle fibers. The laminin alpha 2 chain is absent or drastically reduced in a subgroup of congenital muscular dystrophy patients, and in the severely affected dystrophic dy/dy mouse. We previously reported that heterogeneous primary mouse muscle cell cultures conferred laminin alpha 2 chain expression in dy/dy mice muscles upon cell transplantation. In the present study we investigated whether pure myoblast cell lines were able to confer laminin alpha 2 chain expression in vivo. We observed that: (1) xeno-transplantation of non-immortalized human myoblast in SCID mouse muscles allows human laminin alpha 2 chain expression; (2) allotransplantation of the permanent G8 mouse myoblast cell line in dy/dy muscles allows the expression of the murine laminin alpha 2 chain; and (3) allo-transplantation of the D7 dystrophic dy/dy cell line allows the formation of new and hybrid muscle fibers in dy/dy muscle in the absence of laminin alpha 2 chain expression. We conclude that normal myoblasts are able to restore the expression of an extracellular skeletal muscle protein and that the absence of laminin-2 does not prevent transplanted muscle cells from participating in the formation of myofibers. Myoblasts are, therefore, attractive tools for further exploration of gene complementation strategies in the animal models of congenital muscular dystrophy.
authors.affiliation: Unité de Médecine Génétique et Moléculaire, Centre Hospitalier de l'Université Laval, Québec, Canada.
authors.forename: J T
authors.initials: JT
authors.lastname: Vilquin
authors.forename: B
authors.initials: B
authors.lastname: Guérette
authors.forename: J
authors.initials: J
authors.lastname: Puymirat
authors.forename: D
authors.initials: D
authors.lastname: Yaffe
authors.forename: F M
authors.initials: FM
authors.lastname: Tomé
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
authors.forename: M
authors.initials: M
authors.lastname: Fiszman
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
authors.forename: J P
authors.initials: JP
authors.lastname: Tremblay
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016189:Dystrophin / Q000032:analysis / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000628:therapy; D014411:Neoplastic Stem Cells; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
chemical_list: D016189:Dystrophin; D016326:Extracellular Matrix Proteins; D007797:Laminin; D009124:Muscle Proteins; C102645:laminin alpha 2