Reversal of non-hydroxy:alpha-hydroxy galactosylceramide ratio and unstable myelin in transgenic mice overexpressing UDP-galactose:ceramide galactosyltransferase

J Neurochem. 2005 Jul;94(2):469-81. doi: 10.1111/j.1471-4159.2005.03221.x.


The sphingolipids galactosylceramide and sulfatide are important for the formation and maintenance of myelin. Transgenic mice overexpressing the galactosylceramide synthesizing enzyme UDP-galactose:ceramide galactosyltransferase in oligodendrocytes display an up to four-fold increase in UDP-galactose:ceramide galactosyltransferase activity, which correlates with an increase in its products monogalactosyl diglyceride and non-hydroxy fatty acid-containing galactosylceramide. Surprisingly, however, we observed a concomitant decrease in alpha-hydroxylated galactosylceramide such that total galactosylceramide in transgenic mice was almost unaltered. These data suggest that UDP-galactose:ceramide galactosyltransferase activity does not limit total galactosylceramide level. Furthermore, the predominance of alpha-hydroxylated galactosylceramide appeared to be determined by the extent to which non-hydroxylated ceramide was galactosylated rather than by the higher affinity of UDP-galactose:ceramide galactosyltransferase for alpha-hydroxy fatty acid ceramide. The protein composition of myelin was unchanged with the exception of significant up-regulation of the myelin and lymphocyte protein. Transgenic mice were able to form myelin, which, however, was apparently unstable and uncompacted. These mice developed a progressive hindlimb paralysis and demyelination in the CNS, demonstrating that tight control of UDP-galactose:ceramide galactosyltransferase expression is essential for myelin maintenance.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Behavior, Animal / physiology
  • Blotting, Northern / methods
  • Blotting, Western / methods
  • Brain / anatomy & histology
  • Brain / metabolism
  • Chromatography, Thin Layer / methods
  • Fatty Acids / metabolism
  • Galactosylceramides / metabolism*
  • Galactosyltransferases / genetics
  • Galactosyltransferases / metabolism*
  • Ganglioside Galactosyltransferase
  • Gene Expression Regulation, Developmental / physiology*
  • In Situ Hybridization / methods
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron, Transmission / methods
  • Motor Activity / genetics
  • Myelin Sheath / metabolism*
  • Myelin-Associated Glycoprotein / metabolism
  • Optic Nerve / ultrastructure
  • Psychosine / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Rotarod Performance Test / methods
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods


  • Fatty Acids
  • Galactosylceramides
  • Myelin-Associated Glycoprotein
  • RNA, Messenger
  • Psychosine
  • Galactosyltransferases
  • Ugt8a protein, mouse
  • Ganglioside Galactosyltransferase