Laminin in Animal Models for Muscular Dystrophy Defect of Laminin M in Skeletal and Cardiac Muscles and Peripheral Nerve of the Homozygous Dystrophic dy/dy Mice.

Abstract

We have immunocytochemically shown a significant reduction in the amount of laminin M (or merosin; a tissue-restricted basal lamina protein expressed in striated muscle, Schwann cells, and placental trophoblast) in the skeletal muscle of Fukuyama type congenital muscular dystrophy (FCMD).1) To inquire into the role of laminin M in the process of muscular dystrophies, we examined laminin M in several animal models that cause muscular dystrophy. Immunofluorescent, immunoblotting, and electron microscopic analyses have revealed that laminin M is missing from skeletal and cardiac muscles and peripheral nerve in the affected homozygous C57BL/6J-dy/dy mice, but not in the non-affected heterozygous Dy/dy and the other dystrophic animal models including mdx mice, BIO 14.6 hamsters, and line 413 chickens. In the dy/dy mice, laminin M mRNA is not detected by Northern blotting, but becomes detectable by RT-PCR amplification. Other components of the basal lamina such as laminin B, beta-integrin, type IV collagen, and fibronectin are normally expressed in all animals examined, including the dy/dy mice. These observations strongly suggest that laminin M defect is primarily responsible for the pathogenesis of muscle fiber damage and dysmyelination of the dystrophic dy/dy mice.