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The Journal of Neuroscience, March 15, 1998, 18(6):1953-1962
Myelin-Associated Glycoprotein Is a Myelin Signal that Modulates the Caliber of Myelinated Axons
Xinghua Yin1, Thomas O. Crawford2, John W. Griffin2, 3, Pang-hsien Tu4, Virginia M.-Y. Lee4, Chumei Li5, John Roder5, and Bruce D. Trapp1 1 Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, Departments of 2 Neurology and 3 Neurosciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, 4 Department of Pathology and Laboratory Medicine, Division of Anatomic Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, and 5 Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario M5G 1X5 Canada
Myelination increases neuronal conduction velocity through its insulating properties and an unidentified extrinsic effect that increases axonal caliber. Although it is well established that demyelination can cause axonal atrophy, the myelin molecule that regulates axonal caliber is not known. Loss of the structural proteins of compact peripheral nervous system (PNS) myelin, P0 protein, and myelin basic protein does not lead to axonal atrophy. This study demonstrates that mice with a null mutation of the myelin-associated glycoprotein (MAG) gene have a chronic atrophy of myelinated PNS axons that results in paranodal myelin tomaculi and axonal degeneration. Absence of MAG was correlated with reduced axonal calibers, decreased neurofilament spacing, and reduced neurofilament phosphorylation. Because axonal atrophy and degeneration in MAG-deficient mice occur in the absence of inflammation, hypomyelination, significant demyelination-remyelination, or gain of function mutations, these data support a functional role for MAG in modulating the maturation and viability of myelinated axons.
Key words: myelin-associated glycoprotein; axonal atrophy; neurofilament phosphorylation; axonal caliber; neurofilament spacing; paranodal tomaculi
Copyright © 1998 Society for Neuroscience 0270-6474/98/1861953-10$05.00/0
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