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Cell-specific deletion of glucosylceramide synthase in brain leads to severe neural defects after birth

  • Sialic acid-containing glycosphingolipids, i.e., gangliosides, constitute a major component of neuronal cells and are thought to be essential for brain function. UDP-glucose:ceramide glucosyltransferase (Ugcg) catalyzes the initial step of glycosphingolipid (GSL) biosynthesis. To gain insight into the role of GSLs in brain development and function, a cell-specific disruption of Ugcg was performed as indicated by the absence of virtually all glucosylceramide-based GSLs. Shortly after birth, mice showed dysfunction of cerebellum and peripheral nerves, associated with structural defects. Axon branching of Purkinje cells was significantly reduced. In primary cultures of neurons, dendritic complexity was clearly diminished, and pruning occurred early. Myelin sheaths of peripheral nerves were broadened and focally severely disorganized. GSL deficiency also led to a down-regulation of gene expression sets involved in brain development and homeostasis. Mice died approximately 3 weeks after birth. These results imply that GSLs are essential for brain maturation.

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Document Type:Article
Author:Richard Jennemann, Roger Sandhoff, Shijun Wang, Eva Kiss, Norbert Gretz, Cecilia Zuliani, Ana Martin-Villalba, Richard Jäger, Hubert Schorle, Marc Kenzelmann, Mahnaz Bonrouhi, Herbert Wiegandt, Hermann-Josef Gröne
Parent Title (English):Proc Natl Acad Sci USA (Proceedings of the National Academy of Sciences of the United States of America)
First Page:12459
Last Page:12464
Publisher:National Academy of Sciences
Date of first publication:2005/08/18
Departments, institutes and facilities:Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Entry in this database:2018/07/14