Transgenic Expression of Laminin α1 Chain Does Not Prevent Muscle Disease in the mdx Mouse Model for Duchenne Muscular Dystrophy

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 alpha 1 chain in mdx animals, resulting in lanainin-111 heterotrimer formation in mdx muscle, does not improve the dystrophic phenotype. The mdx mice overexpressing laminin-111 (mdxLM alpha 1) 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 alpha 7 is not beneficial for mdxLM alpha 1 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. (Am J Pathol 2011, 178:1728-1737; DOI: 10.1016/j.ajpath.2010.12.030)