| First Author | Fewou SN | Year | 2005 |
| Journal | J Neurochem | Volume | 94 |
| Issue | 2 | Pages | 469-81 |
| PubMed ID | 15998297 | Mgi Jnum | J:99421 |
| Mgi Id | MGI:3582125 | Doi | 10.1111/j.1471-4159.2005.03221.x |
| Citation | Fewou SN, et al. (2005) Reversal of non-hydroxy : alpha-hydroxy galactosylceramide ratio and unstable myelin in transgenic mice overexpressing UDP-galactose : ceramide galactosyltransferase. J Neurochem 94(2):469-81 |
| abstractText | Abstract 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. |
