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Inactivation of ceramide synthase 6 in mice results in an altered sphingolipid metabolism and behavioral abnormalities

Item Type:Article
Title:Inactivation of ceramide synthase 6 in mice results in an altered sphingolipid metabolism and behavioral abnormalities
Creators Name:Ebel, P. and Vom Dorp, K. and Petrasch-Parwez, E. and Zlomuzica, A. and Kinugawa, K. and Mariani, J. and Minich, D. and Ginkel, C. and Welcker, J. and Degen, J. and Eckhardt, M. and Dere, E. and Doermann, P. and Willecke, K.
Abstract:The N-acyl chain length of ceramides is determined by the specificity of different ceramide synthases (CerS). The CerS family in mammals consists of six members with different substrate specificities and expression patterns. We have generated and characterized a mouse line harboring an enzymatically inactive ceramide synthase 6 (CerS6KO) gene and lacz reporter cDNA coding for beta-galactosidase directed by the CerS6 promoter. These mice display a decrease in C16:0 containing sphingolipids. Relative to wild type tissues the amount of C16:0 containing sphingomyelin in kidney is approximately 35%, whereas we find a reduction of C16:0 ceramide content in the small intestine to about 25%. The CerS6KO mice show behavioral abnormalities including a clasping abnormality of their hind limbs and a habituation deficit. LacZ reporter expression in the brain reveals CerS6 expression in hippocampus, cortex, and the Purkinje cell layer of the cerebellum. Using newly developed antibodies that specifically recognize the CerS6 protein we show that the endogenous CerS6 protein is N-glycosylated and expressed in several tissues of mice, mainly kidney, small and large intestine, and brain.
Keywords:Brain, Ceramide, Glycerophospholipid, Kidney, Mass Spectrometry (MS), CerS6, Lass6, Ceramide Synthase Activity, Sphingomyelin, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:288
Number:29
Page Range:21433-21447
Date:19 July 2013
Official Publication:https://doi.org/10.1074/jbc.M113.479907
PubMed:View item in PubMed

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