Mice deficient for the epidermal Dermokine β and γ display transient cornification defects

Abstract

Expression of the human Dermokine gene (DMKN) leads to the production of four isoform families. The secreted α, β and γ isoforms share epidermis-restricted expression pattern, with Dmkn β/γ being specifically expressed by the granular keratinocytes. The δ isoforms are intracellular and ubiquitous. Our in-depth characterization of Dmkn expression in mouse skin revealed it was less complex than in Human. In particular, messengers coding for the δ family were absent. Homozygous Dmkn(β/γ)−/− mice showed no obvious phenotype but only a temporary scaly skin during the first week of life. The Dmkn(β/γ)−/− pups had smaller keratohyalin granules and their cornified envelopes were more sensitive to mechanical stress. At the molecular level, amounts of profilaggrin and filaggrin monomers were reduced whereas amino-acid components of the natural moisturizing factor were increased. In addition, the electrophoretic mobility of involucrin was modified, suggesting post-translational modifications. Finally, the Dmkn(β/γ)−/− mice strongly overexpressed Dmkn α. These data are evocative of compensatory mechanisms, relevant with the temporary phenotype. Overall, we improved the knowledge of Dmkn expression in mouse and highlighted a role for Dmkn β/γ in cornification.