title: Transgenic expression of Laminin α1 chain does not prevent muscle disease in the mdx mouse model for Duchenne muscular dystrophy.
abstract: Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder, and one of the most frequently encountered, but one for which there is as yet no treatment. Laminin-111 protein therapy was recently shown to be a promising approach to prevent muscle disease in the mdx mouse model of DMD. The present study demonstrated that transgenic expression of laminin α1 chain in mdx animals, resulting in laminin-111 heterotrimer formation in mdx muscle, does not improve the dystrophic phenotype. The mdx mice overexpressing laminin-111 (mdxLMα1) display features of mdx littermates: dystrophic pattern of muscle biopsy, elevated creatine kinase levels, reduced muscle strength, and decreased sarcolemmal integrity. Increased expression of integrin α7 is not beneficial for mdxLMα1 muscle, and components of the dystrophin-glycoprotein complex are not restored at the sarcolemma on laminin-111 overexpression. In summary, further studies are needed to verify the functionality of laminin-111 protein therapy in DMD and to describe the molecular events resulting from this approach.
authors: Department of Experimental Medical Science, Muscle Biology Unit, University of Lund, Lund, Sweden. kinga.gawlik@med.lu.se.
authors: Kinga I
authors: KI
authors: Gawlik
authors: Bruno M
authors: BM
authors: Oliveira
authors: Madeleine
authors: M
authors: Durbeej
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001706:Biopsy; D003402:Creatine Kinase / Q000378:metabolism; D005070:Evans Blue / Q000494:pharmacology; D005786:Gene Expression Regulation; D007797:Laminin / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D009132:Muscles / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D019076:Transgenes
chemical_list: D007797:Laminin; C084098:laminin A; D005070:Evans Blue; D003402:Creatine Kinase