Schwann Cell Myelination Occurred Without Basal Lamina Formation in Laminin 2 Chain-Null Mutant (dy 3K /dy 3K ) Mice MASAHIRO NAKAGAWA, 1,4 YUKO MIYAGOE-SUZUKI, 2 KOJI IKEZOE, 1,5 YUHEI MIYATA, 3 IKUYA NONAKA, 1 KIYONORI HARII, 4 AND SHIN’ICHI TAKEDA 2 * 1 Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan 2 Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan 3 Department of Pharmacology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan 4 Department of Plastic, Reconstructive and Aesthetic Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan KEY WORDS knockout mouse; peripheral nerve; merosin; laminin M chain; extra- cellular matrix ABSTRACT The laminin 2 chain is a major component of basal lamina in both skeletal muscle and the peripheral nervous system. Laminin 2 chain deficiency causes merosin-deficient congenital muscular dystrophy, which affects not only skeletal mus- cles, but also the peripheral and central nervous systems. It has been reported that the formation of basal lamina is required for myelination in the peripheral nervous system. In fact, the spinal root of dystrophic mice (dy/dy mice), whose laminin 2 chain expres- sion is greatly reduced, shows lack of basal lamina and clusters of naked axons. To investigate the role of laminin 2 chain and basal lamina in vivo, we examined the peripheral nervous system of dy 3K /dy 3K mice, which are null mutants of laminin 2 chain. The results indicate the presence of myelination although Schwann cells lacked basal lamina in the spinal roots of dy 3K /dy 3K mice, suggesting that basal lamina is not an absolute requirement for myelination in vivo. Immunohistochemically, the expres- sion of laminin 4 chain was increased and laminin 5 chain was preserved in the endoneurium of the spinal root. Laminin 4 and 5 chains may play the critical role in myelination instead of laminin 2 chain in dy 3K /dy 3K mice. In addition, the motor conduction velocity of the sciatic nerve was significantly reduced compared with that of wild-type littermate. This reduction in conduction velocity may be due to small axon diameter, thin myelin sheath and the patchy disruption of the basal lamina of the nodes of Ranvier in dy 3K /dy 3K mice. GLIA 35:101–110, 2001. © 2001 Wiley-Liss, Inc. INTRODUCTION Laminin-2 (2, 1, and 1 chains), also known as merosin, is a major component of the basal lamina proteins in skeletal muscle and the peripheral nervous system (PNS). Laminin 2 chain is expressed in the endoneurial basal lamina surrounding the myelin sheath of the nerve fibers (Patton et al., 1997). Laminin 2 chain binds to -dystroglycan, the outer membrane glycoprotein of Schwann cells, and -dystroglycan binds to agrin, one of the basal lamina proteins of Schwann cells and neuromuscular junctions (Yamada et al., 1996; Matsumura et al., 1997). Laminin 2 chain Koji Ikezoe is currently at the Department of Neurology, Neurological Insti- tute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812- 8585, Japan. *Correspondence to: Shin’ichi Takeda, Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-higashi, Kodaira, Tokyo, 187-8502, Japan. E-mail: takeda@ncnp.go.jp Received 9 February 2001; Accepted 15 May 2001 Published online 00 Month 2001 GLIA 35:101–110 (2001) © 2001 Wiley-Liss, Inc.