title: Absence of oligodendroglial glucosylceramide synthesis does not result in CNS myelin abnormalities or alter the dysmyelinating phenotype of CGT-deficient mice.
abstract: To examine the function of glycosphingolipids (GSLs) in oligodendrocytes, the myelinating cells of the central nervous system (CNS), mice were generated that lack oligodendroglial expression of UDP-glucose ceramide glucosyltransferase (encoded by Ugcg). These mice (Ugcg(flox/flox);Cnp/Cre) did not show any apparent clinical phenotype, their total brain and myelin extracts had normal GSL content, including ganglioside composition, and myelin abnormalities were not detected in their CNS. These data indicate that the elimination of gangliosides from oligodendrocytes is not detrimental to myelination. These mice were also used to asses the potential compensatory effect of hydroxyl fatty acid glucosylceramide (HFA-GlcCer) accumulation in UDP-galactose:ceramide galactosyltransferase (encoded by Cgt, also known as Ugt8a) deficient mice. At postnatal day 18, the phenotypic characteristics of the Ugcg(flox/flox);Cnp/Cre;Cgt(-/-) mutants, including the degree of hypomyelination, were surprisingly similar to that of Cgt(-/-) mice, suggesting that the accumulation of HFA-GlcCer in Cgt(-/-) mice does not modify their phenotype. These studies demonstrate that abundant, structurally intact myelin can form in the absence of glycolipids, which normally represent over 20% of the dry weight of myelin.
authors.affiliation: Department of Neurology, The Jack Miller Center for Peripheral Neuropathy, The University of Chicago, Illinois, USA.
authors.forename: Laleh
authors.initials: L
authors.lastname: Saadat
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Dupree
authors.forename: John
authors.initials: J
authors.lastname: Kilkus
authors.forename: Xianlin
authors.initials: X
authors.lastname: Han
authors.forename: Maria
authors.initials: M
authors.lastname: Traka
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
authors.forename: Glyn
authors.initials: G
authors.lastname: Dawson
authors.forename: Brian
authors.initials: B
authors.lastname: Popko
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology; D002493:Central Nervous System Diseases / Q000473:pathology / Q000503:physiopathology*; D051147:Ganglioside Galactosyltransferase / Q000235:genetics / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism; D005963:Glucosylceramides / Q000378:metabolism*; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D014531:Uridine Diphosphate Galactose / Q000378:metabolism
chemical_list: D005732:Gangliosides; D005963:Glucosylceramides; D014531:Uridine Diphosphate Galactose; D005964:Glucosyltransferases; C511214:Ugt8a protein, mouse; D051147:Ganglioside Galactosyltransferase; C023246:ceramide glucosyltransferase
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