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Generation and analysis of mutant mouse models to study pathophysiological roles of KLK5 and KLK7 in epidermis
 Kašpárek, Petr ; Sedláček, Radislav (advisor) ; Stopka, Pavel (referee) ; Machoň, Ondřej (referee)
Kallikrein-related peptidases (KLKs) constitute a family of closely related serine proteases encoded by genes clustered in one chromosomal locus. KLKs are widely expressed in a variety of tissues and numerous in vitro experiments suggest their important roles in many physiological and pathological processes. However, the biological roles of KLKs in vivo are often obscured mainly due to unavailability of suitable animal models. Although gene deficient mouse models were generated for several KLK genes, they had limited use for understanding the roles of individual proteases in the complex environment in vivo. One of the main obstacles which hampers in vivo analysis is partial functional overlap between some KLKs. This makes traditional single-gene deficient animal models an inadequate tool to address the biological impact of the gene deficiency as compensatory mechanisms often result in a lack of phenotype. In this work, we used the transcription activator-like effector nuclease (TALEN) technology to generate several novel mutant mouse models to study the complex KLK proteolytic pathways and their roles in healthy organism and in disease. We prepared a novel mouse model for Netherton syndrome (NS), an autosomal recessive skin disorder caused by mutation in the gene SPINK5, which encodes the KLK-inhibitor...
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