MYELIN GALACTOLIPIDS ARE ESSENTIAL FOR PROPER NODE OF RANVIER FORMATION IN THE CNS

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 gala ctosyl transferase (CGT) are incapable of synthesizing these lipids ye t form myelin sheaths that exhibit major and minor dense lines with sp acing comparable to controls, These CGT mutant mice exhibit a severe t remor that is accompanied by hindlimb paralysis. Furthermore, electrop hysiological studies reveal nerve conduction deficits in the spinal co rd of these mutants. Here, using electron microscopic techniques, we d emonstrate ultrastructural myelin abnormalities in the CNS that are co nsistent with the electrophysiological deficits. These abnormalities i nclude altered nodal lengths, an abundance of heminodes, an absence of transverse bands, and the presence of reversed lateral loops, In cont rast to the CNS, no ultrastructural abnormalities and only modest elec trophysiological deficits were observed in the peripheral nervous syst em. Taken together, the data presented here indicate that GalC and sul fatide are essential in proper CNS node and paranode formation and tha t these lipids are important in ensuring proper axo-oligodendrocyte in teractions.