title: Partial laminin alpha2 chain restoration in alpha2 chain-deficient dy/dy mouse by primary muscle cell culture transplantation.
abstract: Laminin-2 is a component of skeletal and cardiac basal lamina expressed in normal mouse and human. Laminin alpha2 chain (LAMA2), however, is absent from muscles of some congenital muscular dystrophy patients and the dystrophia muscularis (dy/dy) mouse model. LAMA2 restoration was investigated following cell transplantation in vivo in dy/dy mouse. Allogeneic primary muscle cell cultures expressing the beta-galactosidase transgene under control of a muscular promoter, or histocompatible primary muscle cell cultures, were transplanted into dy/dy mouse muscles. FK506 immunosuppression was used in noncompatible models. All transplanted animals expressed LAMA2 in these immunologically-controlled models, and the degrees of LAMA2 restoration were shown to depend on the age of the animal at transplantation, on muscle pretreatment, and on duration time after transplantation in some cases. LAMA2 did not always colocalize with new or hybrid muscle fibers formed by the fusion of donor myoblasts. LAMA2 deposition around muscle fibers was often segmental and seemed to radiate from the center to the periphery of the injection site. Allogeneic conditionally immortalized pure myogenic cells expressing the beta-galactosidase transgene were characterized in vitro and in vivo. When injected into FK506-immunosuppressed dy/dy mice, these cells formed new or hybrid muscle fibers but essentially did not express LAMA2 in vivo. These data show that partial LAMA2 restoration is achieved in LAMA2-deficient dy/dy mouse by primary muscle cell culture transplantation. However, not all myoblasts, or myoblasts alone, or the muscle fibers they form are capable of LAMA2 secretion and deposition in vivo.
authors.affiliation: Centre de Recherche en Neurobiologie de l'Université Laval, Hôpital de l'Enfant-Jésus, Québec, Canada.
authors.forename: J T
authors.initials: JT
authors.lastname: Vilquin
authors.forename: I
authors.initials: I
authors.lastname: Kinoshita
authors.forename: B
authors.initials: B
authors.lastname: Roy
authors.forename: M
authors.initials: M
authors.lastname: Goulet
authors.forename: E
authors.initials: E
authors.lastname: Engvall
authors.forename: F
authors.initials: F
authors.lastname: Tomé
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
authors.forename: J P
authors.initials: JP
authors.lastname: Tremblay
mesh_terms: D000367:Age Factors; D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D004546:Elapid Venoms / Q000494:pharmacology; D005260:Female; D005720:Gamma Rays; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007797:Laminin / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018485:Muscle Fibers, Skeletal / Q000737:chemistry; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D009137:Muscular Dystrophy, Animal / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D004546:Elapid Venoms; D007166:Immunosuppressive Agents; D007797:Laminin; C005082:notexin; D001616:beta-Galactosidase; D016559:Tacrolimus