Inactivation of Ceramide Synthase 6 in Mice Results in an Altered Sphingolipid Metabolism and Behavioral Abnormalities - Biological Adaptation and Ageing Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2013

Inactivation of Ceramide Synthase 6 in Mice Results in an Altered Sphingolipid Metabolism and Behavioral Abnormalities

Philipp Ebel
  • Fonction : Auteur
Katharina Vom Dorp
  • Fonction : Auteur
Elisabeth Petrasch-Parwez
  • Fonction : Auteur
Armin Zlomuzica
  • Fonction : Auteur
David Minich
  • Fonction : Auteur
Christina Ginkel
  • Fonction : Auteur
Jochen Welcker
  • Fonction : Auteur
Joachim Degen
  • Fonction : Auteur
Matthias Eckhardt
  • Fonction : Auteur
Ekrem Dere
  • Fonction : Auteur
Peter Doermann
  • Fonction : Auteur
Klaus Willecke
  • Fonction : Auteur

Résumé

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 similar to 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.

Dates et versions

hal-01545803 , version 1 (23-06-2017)

Identifiants

Citer

Philipp Ebel, Katharina Vom Dorp, Elisabeth Petrasch-Parwez, Armin Zlomuzica, Kiyoka Kinugawa, et al.. Inactivation of Ceramide Synthase 6 in Mice Results in an Altered Sphingolipid Metabolism and Behavioral Abnormalities. Journal of Biological Chemistry, 2013, 288 (29), pp.21433-21447. ⟨10.1074/jbc.M113.479907⟩. ⟨hal-01545803⟩
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