Inactivation of ceramide synthase 2 catalytic activity in mice affects transcription of genes involved in lipid metabolism and cell division.

Biochim Biophys Acta Mol Cell Biol Lipids 2018 07 10;1863(7):734-749. Epub 2018 Apr 10.

Molecular Genetics, Life and Medical Sciences Institute, University of Bonn, Germany. Electronic address:

The replacement of two consecutive histidine residues by alanine residues in the catalytic center of ceramide synthase 2 in a new transgenic mouse mutant (CerS2 H/A) leads to inactivation of catalytic activity and reduces protein level to 60% of the WT level. We show here by qRT-PCR and transcriptome analyses that several transcripts of genes involved in lipid metabolism and cell division are differentially regulated in livers of CerS2 H/A mice. Thus, very long chain ceramides produced by CerS2 are required for transcriptional regulation of target genes. The hepatocellular carcinomata previously described in old CerS2 KO mice were already present in 8-week-old CerS2 H/A animals and thus are caused by the loss of CerS2 catalytic activity already during early life.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S13881981183005
Publisher Site
http://dx.doi.org/10.1016/j.bbalip.2018.04.006DOI Listing
July 2018

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