Pathologic consequences of epidermal lipase deficiencies

PROJECT SUMMARY/ABSTRACT The biological function of skin enriched lipases (epidermal lipases) K, M and N are not defined. Some people with autosomal recessive congenital ichthyosis harbor disease associated Lipase N mutations, suggesting a clinically relevant role for this protein in skin health. In addition, our recent work indicates lipase M is critical for skin development and function and that epidermal lipase transcripts are reduced in a chronic lesion of atopic dermatitis. These observations suggest epidermal lipases M, N, and, potentially, K, are important for skin development and that defects or deficiencies of one or more of these proteins may contribute to some types of ichthyoses and atopic dermatitis. In light of these observations, the primary goal of this research is to use novel experimental systems to understand the biological consequences of epidermal lipases K, M and N deficiency in skin development and function. The proposed studies will use human skin equivalents lacking expression of individual epidermal lipases (Aim 1) and an inducible lipase M conditional knock out mouse model (Aim 2) to understand the pathologic consequences of epidermal lipase deficiencies. Understanding the consequences of epidermal lipase deficiencies may provide insights into the molecular functions of these proteins and could lead to novel therapies for inherited ichthyoses and atopic dermatitis.