Ceramide synthase 4 deficiency in mice causes lipid alterations in sebum and results in alopecia

神经酰胺 鞘脂 内科学 神经酰胺合酶 内分泌学 表型 生物 化学 细胞生物学 生物化学 医学 细胞凋亡 基因
作者
Philipp Ebel,Silke Imgrund,Katharina vom Dorp,Kristina Hofmann,Helena J. Maier,Helena Drake,Joachim Degen,Peter Dörmann,Matthias Eckhardt,Thomas Franz,Klaus Willecke
出处
期刊:Biochemical Journal [Portland Press]
卷期号:461 (1): 147-158 被引量:62
标识
DOI:10.1042/bj20131242
摘要

Five ceramide synthases (CerS2–CerS6) are expressed in mouse skin. Although CerS3 has been shown to fulfill an essential function during skin development, neither CerS6- nor CerS2-deficient mice show an obvious skin phenotype. In order to study the role of CerS4, we generated CerS4-deficient mice (Cers4−/−) and CerS4-specific antibodies. With these biological tools we analysed the tissue distribution and determined the cell-type specific expression of CerS4 in suprabasal epidermal layers of footpads as well as in sebaceous glands of the dorsal skin. Loss of CerS4 protein leads to an altered lipid composition of the sebum, which is more solidified and therefore might cause progressive hair loss due to physical blocking of the hair canal. We also noticed a strong decrease in C20 1,2-alkane diols consistent with the decrease of wax diesters in the sebum of Cers4−/− mice. Cers4−/− mice at 12 months old display additional epidermal tissue destruction due to dilated and obstructed pilary canals. Mass spectrometric analyses additionally show a strong decrease in C20-containing sphingolipids.
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