COMPOSITION AND BIOPHYSICAL PROPERTIES OF MYELIN LIPID DEFINE THE NEUROLOGICAL DEFECTS IN GALACTOCEREBROSIDE-DEFICIENT AND SULFATIDE-DEFICIENT MICE

Oligodendrocytes and Schwann cell-specific proteins are assembled with a highly ordered membrane lipid bilayer to the myelin sheath of axons , which functions as an insulator and allows rapid saltatory conductio n. We approached the question of the function of the CNS and PNS myeli n-specific galactospingolipids cerebrosides and sulfatides by generati ng a ceramide galactosyltransferase null allelic mouse line (cgt(-/-)) . Galactocerebroside- and sulfatide-deficient myelin loses its insulat ing properties and causes a severe dysmyelinosis that is incompatible with life. Here, we describe the biochemical and biophysical analysis of the myelin lipid bilayer of cgt(-/-) mice. The lipid composition of CNS and PNS myelin of cgt(-/-) mice is seriously perturbed and the sp hingolipid biosynthetic pathway altered. Nonhydroxy and hydroxy fatty acid-substituted glycosylceramides (GlcC) are synthesized by oligodend rocytes and sulfated GlcC in addition in Schwann cells. The monogalact osyldiglyceride fraction is missing in the cgt(-/-) mouse; This new li pid composition can be correlated with the biophysical properties of t he myelin sheath. The deficiency of galactocerebrosides and sulfatides leads to an increased fluidity, permeability, and impaired packing of the myelin lipid bilayer of the internodal membrane system. The loss of the two glycosphingolipid classes causes the breakdown of saltatory conductance of myelinated axons in the cgt(-/-) mouse.