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  -