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Exploring Systemic Functions of Lysosomal Proteases: The Perspective of Genetically Modified Mouse Models

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Proteases: Structure and Function

Abstract

The generation of genetically engineered mouse models (GEM) allows studying the effects of deleting, mutating, or overexpressing proteases and their endogenous inhibitors in a complex living organism. During the past decade this approach has been widely used to investigate endolysosomal proteases, such as the cysteine cathepsins, and their endogenous inhibitors. Here we summarize the findings and discoveries made by the analysis of these GEM in diverse physiological and pathological processes, i.e. skin homeostasis, atherosclerosis, cardiomyopathy, and neurodegeneration. Throughout these diverse subjects we focus on how the normal balance of proteolytic enzymes and their natural inhibitors have been disturbed by the genetic alternations. The phenotypic consequences of these alterations were shown to be highly context-dependent resulting in cell- and tissue-specific pathologies.

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Acknowledgement

The work of the laboratory is supported by the Deutsche Forschungsgemeinschaft SFB 850 Project B7, the Centre of Chronic Immunodeficiency (CCI) Freiburg grant TP8, the Excellence Initiative of the German Federal and State Governments (EXC 294), and the European Union Framework Program (FP7 “MICROENVIMET” No 201279).

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Authors and Affiliations

  1. Institute of Molecular Medicine and Cell Research and Faculty of Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany

    Martina Gansz

  2. Institue of Molecular Medicine and Cell Research, Spemann Graduate School of Biology and Medicine (SGBM) and Faculty of Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany

    Ursula Kern

  3. Institue of Molecular Medicine and Cell Research, and BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg, Freiburg, Germany

    Christoph Peters

  4. Institute of Molecular Medicine and Cell Research and BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg, Stefan Meier Str. 17, Freiburg, 79104, Germany

    Thomas Reinheckel

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  1. Martina Gansz
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Correspondence to Thomas Reinheckel .

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  1. SCHOOL OF ENGINEERING AND SCIENCE, JACOBS UNIVERSITY BREMEN, Bremen, Germany

    Klaudia Brix

  2. Institute of Zoology, Johannes Gutenberg University Mainz, Mainz, Germany

    Walter Stöcker

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Gansz, M., Kern, U., Peters, C., Reinheckel, T. (2013). Exploring Systemic Functions of Lysosomal Proteases: The Perspective of Genetically Modified Mouse Models. In: Brix, K., Stöcker, W. (eds) Proteases: Structure and Function. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0885-7_6

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