Genetic dissection of myelin galactolipid function

The roles that the myelin galactolipids galactocerebroside (GalC) and sulfa tide play in cellular differentiation, myelin formation and maintenance hav e been investigated for nearly 3 decades. During that time the primary appr oach has been to perturb lipid activity using antibodies and chemical agent s in artificial systems. Recently, the isolation of the gene that encodes U DP-galactose:ceramide galactosyltransferase (CGT), the enzyme that catalyze s an essential step in the synthetic pathway of GalC and sulfatide, has ena bled the generation of mice that lack myelin galactolipids. These mice disp lay a severe tremor, hindlimb paralysis and electrophysiological defects. I n addition, the CGT null mutants exhibit: 1) impaired oligodendrocyte diffe rentiation, 2) myelin sheaths that are thin, incompletely compacted and uns table, and 3) structural abnormalities in the nodal and paranodal regions i ncluding disrupted axo-glial junctions. Collectively, these findings sugges t that GalC and sulfatide are essential in myelin formation and maintenance , possibly by mediating intra- and intercellular interactions.