LAMININ IN ANIMAL-MODELS FOR MUSCULAR-DYSTROPHY - DEFECT OF LAMININ-MIN SKELETAL AND CARDIAC MUSCLES AND PERIPHERAL-NERVE OF THE HOMOZYGOUS DYSTROPHIC DY DY MICE/

We have immunocytochemically shown a significant reduction in the amou nt 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 dystroph y (FCMD).1) To inquire into the role of laminin M in the process of mu scular dystrophies, we examined laminin M in several animal models tha t cause muscular dystrophy. Immunofluorescent, immunoblotting, and ele ctron microscopic analyses have revealed that laminin M is missing fro m skeletal and cardiac muscles and peripheral nerve in the affected ho mozygous 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, larninin M mR NA is not detected by Northern blotting, but becomes detectable by RT- PCR amplification. Other components of the basal lamina such as lamini n B, beta-integrin, type IV collagen, and fibronectin are normally exp ressed in all animals examined, including the dy/dy mice. These observ ations strongly suggest that laminin M defect is primarily responsible for the pathogenesis of muscle fiber damage and dysmyelination of the dystrophic dy/dy mice.