Normal ultrastructure, but altered stratum corneum lipid and protein composition in a mouse model for epidermolytic hyperkeratosis

Recently, we established keratin 10-deficient mice, serving as a model for the hyperkeratotic skin disorder epidermolytic hyperkeratosis. The consider able ichthyosis in these mice suggested alterations in terminal differentia tion and in the formation of a functional epidermal barrier. Here, we repor t on the ultrastructural organization and composition of the stratum corneu m lipids and on the expression of two major cornified envelope proteins. El ectron microscopy of ruthenium tetroxide postfixed skin samples demonstrate d a normal extrusion and morphology of lamellar bodies as well as the forma tion of bona fide lamellar layers in neonatal keratin 10-deficient mice. Wh en we studied the composition of the major stratum corneum Lipids, however, we found significant changes. Most importantly, the analysis of ceramide s ubpopulations revealed that the total amount of ceramide 2 was elevated in keratin 10-deficient mice, whereas ceramides 1, 3, 4, and 5 were decreased among total stratum corneum Lipids. The amount of the ceramide precursors s phingomyelin and glucosylceramide was reduced in the stratum corneum withou t accompanying changes in the mRNA coding for acid sphingomyelinase, Notabl y, we found an increased mRNA and protein content for involucrin in neonata l keratin 10-deficient mice, whereas the expression of loricrin was not cha nged. Our data demonstrate that, although the formation of lipid layers in the stratum corneum appeared to be normal, its lipid composition is signifi cantly altered in keratin 10-deficient mice.