THE RELATIONSHIP BETWEEN HYPERPROLIFERATION AND EPIDERMAL THICKENING IN A MOUSE MODEL FOR BCIE

Epidermal thickening is a phenomenon common to many genodermatoses but little is known about the underlying causes. We have recently created a mouse model for the human skill disease bullous congenital ichthyos iform erythroderma by gene targeting. Mice heterozygous for a truncate d keratin 10 gene exhibit acanthosis and hyperkeratosis as seen in the human disease. The degree of epidermal thickening is highly variable, offering a novel opportunity to investigate how epidermal homeostasis is modulated ill keratin disorders by comparing epidermis from differ ent body regions. We have performed bromodeoxyuridine labeling experim ents and detected proliferation antigens by immunohistochemical means to compare proliferation in the epidermis of wild-type and heterozygou s mice. These results have been compared with the expression of epider mal differentiation markers and of the ''hyperproliferation associated '' keratins K6 and K16. These experiments indicated that hyperprolifer ation is only partly responsible for the morphologic changes and that other mechanisms such as decreased desquamation are likely to be invol ved.