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

Abstract：

: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.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Jennemann R,Sandhoff R,Wang S,Kiss E,Gretz N,Zuliani C,Martin-Villalba A,Jäger R,Schorle H,Kenzelmann M,Bonrouhi M,Wiegandt H,Gröne HJ

doi

10.1073/pnas.0500893102

keywords:

subject

Has Abstract

pub_date

2005-08-30 00:00:00

pages

12459-64

issue

35

eissn

0027-8424

issn

1091-6490

pii

0500893102

journal_volume

102

pub_type

杂志文章

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