*Molecular Genetics, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
†Institute of Molecular Physiology and Biotechnology of Plants, University of Bonn, 53115 Bonn, Germany.
Biochem J. 2014 Jul 1;461(1):147-58. doi: 10.1042/BJ20131242.
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.
五种神经酰胺合酶（CerS2-CerS6）在小鼠皮肤中表达。虽然已经表明 CerS3 在皮肤发育过程中具有重要功能，但 CerS6- 和 CerS2 缺陷型小鼠均没有明显的皮肤表型。为了研究 CerS4 的作用，我们生成了 CerS4 缺陷型小鼠（Cers4-/-）和 CerS4 特异性抗体。利用这些生物学工具，我们分析了组织分布，并确定了 CerS4 在足垫的表皮上层和背部皮肤的皮脂腺中的细胞类型特异性表达。CerS4 蛋白的缺失导致皮脂的脂质组成发生改变，变得更加凝固，因此可能由于毛发通道的物理阻塞而导致逐渐脱发。我们还注意到，由于皮脂中蜡二酯的减少，C20 1,2-烷二醇的含量明显减少。12 个月大的 Cers4-/- 小鼠由于扩张和阻塞的毛囊道而显示出额外的表皮组织破坏。质谱分析还显示，含有 C20 的神经鞘脂的含量明显减少。
