Absence of oligodendroglial glucosylceramide synthesis does not result in CNS myelin abnormalities or alter the dysmyelinating phenotype of CGT‐deficient mice
Open accessAbstract
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. © 2009 Wiley‐Liss, Inc.
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Prior work indicates that the overwhelming majority of brain hexosylceramides are galactosylceramides (galactocerebrosides) rather than glucocerebrosides.
“prior work indicates that the overwhelming majority of brain hexosylceramides are galactosylceramides (galactocerebrosides) rather than glucocerebrosides [57, 58].”
From PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain (2026) · cites this paper as [58]
The Introduction (page unavailable) says myelin galactolipids normally make up a considerable fraction of myelin, and the Results (page unavailable) detect GalCer in total-brain and myelin extracts. The paper does not establish that the overwhelming majority of brain hexosylceramides are GalCer rather than GlcCer; its statement about myelin is narrower than the claimed brain-wide comparison. (LLM, conf=0.78)
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- Authors
- Saadat, L., Dupree, J. L., Kilkus, J., Han, X., Traka, M., Proia, R. L., Dawson, G., & Popko, B.
- Affiliations
- University of Chicago (US)
- Virginia Commonwealth University (US)
- Washington University in St. Louis (US)
- National Institutes of Health (US)
- Corresponding author
- Popko, Brian
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2009-08-24
- Volume
- 58
- Issue
- 4
- Pages
- 391-398
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- PMC
- PMC2807477
- OpenAlex
- W2146242620
- Cited by
- 61
- References
- 38
- Citations by year
- 2026: 2 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 7 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 1 · 2014: 11 · 2013: 4 · 2012: 4
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG023168, AG23168)
- National Institute of Neurological Disorders and Stroke (P30NS047463, R01NS036866, NS027336, NS036866, R01NS027336)
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Keywords
- oligodendrocytes, myelination, glycosphingolipids, gangliosides, UGCG, UDP-galactose:ceramide galactosyltransferase, CGT, hypomyelination, myelin composition, central nervous system myelin
- MeSH terms
- Animals, Brain, Central Nervous System Diseases, Gangliosides, Glucosylceramides, Glucosyltransferases, Mice, Transgenic, Myelin Sheath, Oligodendroglia, Spinal Cord, Uridine Diphosphate Galactose, Mice, Knockout, Ganglioside Galactosyltransferase, Mice
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