DEMYELINATION AND ALTERED EXPRESSION OF MYELIN-ASSOCIATED GLYCOPROTEIN ISOFORMS IN THE CENTRAL-NERVOUS-SYSTEM OF GALACTOLIPID-DEFICIENT MICE

Vertebrate myelin is enriched in the lipid galactocerebroside (GalC) a nd its sulfated derivated sulfatide, To understand the in vivo functio n of these lipids, we analyzed myelination in mice that contain a null mutation in the gene encoding UDP-galactose:ceramide galactosyltransf erase, the enzyme responsible for catalyzing the final step in GalC sy nthesis. Galactolipid-deficient myelin is regionally unstable and prog ressively degenerates. At postnatal day 30, demyelination is restricte d to the midbrain and hindbrain, but by postnatal day 90, it spreads t hroughout the central nervous system. Activated microglial cells and r eactive astrocytes appear with the loss of myelin in older animals, No netheless, major myelin protein gene mRNA levels are normal throughout the life of these animals, suggesting that widespread oligodendrocyte death is not the primary cause of demyelination, The developmental sw itch in myelin-associated glycoprotein isoform expression, however, do es not occur normally in these mice, suggesting an alteration in oligo dendrocyte maturation. Taken together, these findings indicate that Ga lC and sulfatide are required for the long-term maintenance of myelin and that their absence may have subtle effects on the development of o ligodendrocytes, (C) 1998 Wiley-Liss,Inc.