TY - JOUR A1 - Jennemann, Richard A1 - Sandhoff, Roger A1 - Wang, Shijun A1 - Kiss, Eva A1 - Gretz, Norbert A1 - Zuliani, Cecilia A1 - Martin-Villalba, Ana A1 - Jäger, Richard A1 - Schorle, Hubert A1 - Kenzelmann, Marc A1 - Bonrouhi, Mahnaz A1 - Wiegandt, Herbert A1 - Gröne, Hermann-Josef T1 - Cell-specific deletion of glucosylceramide synthase in brain leads to severe neural defects after birth T2 - Proc Natl Acad Sci USA (Proceedings of the National Academy of Sciences of the United States of America) N2 - 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. Y1 - 2005 UR - https://pub.h-brs.de/frontdoor/index/index/docId/3747 SN - 0027-8424 VL - 102 IS - 35 SP - 12459 EP - 12464 PB - National Academy of Sciences ER -