Relationship between time-dependent epidermal ceramide composition changes and skin barrier function in adult mice.

Ceramides, especially acylceramides and protein-bound ceramides, are important for skin barrier formation. However, due to the neonatal lethality of knockout (KO) of the genes involved in the production of these ceramides, the effects of their KO in adult mice have been unclear. To investigate these effects, we created mice with tamoxifen-inducible conditional KO of the fatty acid elongase Elovl1. Following tamoxifen administration, acylceramide levels began to decrease from day 5. On day 10, impaired formation of lipid lamellae and thickening of the epidermis were observed. On day 15, protein-bound ceramide levels were substantially reduced and transepidermal water loss was increased. Changes in quantities of ceramides other than acylceramides and protein-bound ceramides and shortening of their fatty acid moieties were also observed, but time courses differed among ceramide classes. RNA sequencing revealed changes in the expression levels of genes involved in ceramide metabolism and keratinocyte proliferation and differentiation in Elovl1 conditional-KO mice. In summary, this study reveals that acylceramides and protein-bound ceramides are important for maintaining the skin barrier in adults, although they are not essential for survival. We also observed compensatory responses toward reduced skin barrier function, such as changes in gene expression, epidermal morphology, and ceramide composition.