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The Journal of Neuroscience, March 1, 1998, 18(5):1642-1649

Myelin Galactolipids Are Essential for Proper Node of Ranvier Formation in the CNS

Jeffrey L. Dupree¹, Timothy Coetzee¹, Andrew Blight², Kinuko Suzuki^{1, 3}, and Brian Popko^{1, 4, 5}

¹ Neuroscience Center, ² Department of Surgery, Division of Neurosurgery, ³ Department of Pathology and Laboratory Medicine, ⁴ Department of Biochemistry and Biophysics, and ⁵ Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599

The vertebrate myelin sheath is greatly enriched in the galactolipids galactocerebroside (GalC) and sulfatide. Mice with a disruption in the gene that encodes the biosynthetic enzyme UDP-galactose:ceramide galactosyl transferase (CGT) are incapable of synthesizing these lipids yet form myelin sheaths that exhibit major and minor dense lines with spacing comparable to controls. These CGT mutant mice exhibit a severe tremor that is accompanied by hindlimb paralysis. Furthermore, electrophysiological studies reveal nerve conduction deficits in the spinal cord of these mutants. Here, using electron microscopic techniques, we demonstrate ultrastructural myelin abnormalities in the CNS that are consistent with the electrophysiological deficits. These abnormalities include altered nodal lengths, an abundance of heminodes, an absence of transverse bands, and the presence of reversed lateral loops. In contrast to the CNS, no ultrastructural abnormalities and only modest electrophysiological deficits were observed in the peripheral nervous system. Taken together, the data presented here indicate that GalC and sulfatide are essential in proper CNS node and paranode formation and that these lipids are important in ensuring proper axo-oligodendrocyte interactions.

Key words: node of Ranvier; galactocerebroside; sulfatide; myelin; UDP galactose:ceramide galactosyl transferase; axo-glial interaction

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Copyright © 1998 Society for Neuroscience  0270-6474/98/1851642-08$05.00/0

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