GALACTOLIPIDS IN THE FORMATION AND FUNCTION OF THE MYELIN SHEATH

Among the most abundant components of myelin are the galactolipids gal actocerebroside (GalC) and sulfatide. In spite of this abundance, the roles that these molecules play in the myelin sheath are not well unde rstood. Until recently, our concept of GalC and sulfatide functions ha d been principally defined by immunological and chemical perturbation studies that implicate these lipids in oligodendrocyte differentiation , myelin formation, and myelin stability. Recently, however, genetic s tudies have allowed us to re-analyze the functions of these lipids. Tw o laboratories have independently generated mice that are incapable of synthesizing either GalC or sulfatide by inactivating the gene encodi ng the enzyme UDP-galactose:ceramide galactosyltransferase (CGT), whic h is required for myelin galactolipid synthesis. These galactolipid-de ficient animals exhibit a severe tremor, hindlimb paralysis, and displ ay electrophysiological deficits in both the central and peripheral ne rvous systems. In addition, ultrastructural studies have revealed hypo myelinated white matter tracts with unstable myelin sheaths and a vari ety of myelin abnormalities including altered node length, reversed la teral loops, and compromised axo-oligodendrocytic junctions. Collectiv ely, these observations indicate that cell-cell interactions, which ar e essential in the formation and maintenance of a properly functioning myelin sheath, are compromised in these galactolipid-deficient mice. Microsc. Res. Tech. 41:431-440, 1998. a 1998 Wiley-Liss. Inc.