Generation of transgenic mouse model to study biological role of KLK5 in epidermis

Abstract

A number of studies provide strong evidence that KLK5 is one of the most important serine proteases in the epidermis and is involved in processes such as desquamation, processing of antimicrobial peptides or induction of inflammatory reaction. The role of KLK5 has been deduced from in vitro experiments and thus its functions should be verified in vivo. This work aimed to develop a specific tissue targeting strategy to study the role of murine kallikreins in the epidermal compartment in vivo and to generate a transgenic model overexpressing mKlk5 in the mouse epidermis. Using the modified promoter of human involucrin, transgenic mice expressing the fluorescent marker, tdTomato, were generated in the first step. This transgenic reporter mouse showed specific targeting pattern of the reporter in the upper epidermal layers and, thus, the modified involucrin promoter could be employed for targeting further gene of interest in the differentiated epidermal compartment. In the second step transgenic mouse lines expressing murine kallikrein 5 were successfully generated. Among them two lines exhibited approximately 6-9 fold overexpression at the mRNA and protein levels, however it appeared that the immature protease was not activated under normal healthy conditions. Therefore two models of epidermal..