Open AccessCell-specific deletion of glucosylceramide synthase in brain leads to severe neural defects after birth
Author(s) -
Richard Jennemann,
Roger Sandhoff,
Shijun Wang,
Éva Kiss,
Norbert Gretz,
Cecilia Zuliani,
Ana MartinVillalba,
Richard Jäger,
Hubert Schorle,
Marc Kenzelmann,
Mahnaz Bonrouhi,
Herbert Wiegandt,
Hermann Josef Gröne
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0500893102
Subject(s) - ceramide , biology , ganglioside , glycosphingolipid , glycosyltransferase , glycolipid , sphingolipid , biochemistry , cerebellum , sialic acid , myelin , microbiology and biotechnology , central nervous system , gene , neuroscience , apoptosis
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.