SUPPRESSED UDP-GALACTOSE-CERAMIDE GALACTOSYLTRANSFERASE AND MYELIN PROTEIN MESSENGER-RNA IN TWITCHES MOUSE-BRAIN

The developmental changes in expression of steady-state mRNA that enco de proteins that are important for myelination (myelin basic protein, myelin-associated glycoprotein, proteolipid protein, UDP-galactose: ce ramide galactosyltransferase) and glial fibrillary acidic protein were investigated in the brain of the twitcher mouse, a model of human glo boid cell leukodystrophy, This disease is caused by a mutation in the gene encoding the lysosomal enzyme, galactosylceramidase, which cataly zes the degradation of the myelin lipid galactosylceramide. Before pos tnatal day (PND) 20, the levels of myelin protein mRNA were similar in twitcher and normal mice, With progression of demyelination after PND 25-30, myelin protein mRNA levels gradually decreased, The period of maximum expression of the myelin protein genes in twitcher mice was, h owever, similar to that of normal control mice, mRNA levels for the ge ne that encodes the enzyme UDP-galactose:ceramide galactosyltransferas e which is responsible for catalyzing the final step in galactosylcera mide synthesis, was exceptionally downregulated from the early stages of the disease, The increase of glial fibrillary acidic protein (GFAP) mRNA levels preceded morphological evidence of demyelination. (C) 199 8 Wiley-Liss. Inc.