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

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. Abbreviations: CerS, ceramide synthase(s); FA2H, fatty acid 2-hydroxylase; NLS, nuclear localization sequence; P, postnatal day; Scd1, stearoyl-CoA desaturase 1; TBS-T, TBS containing 0.1% Tween