Central mouse generation, phenotyping and imaging

• Applicants: Professorin Dr. Katarzyna Bozek; Dr. Astrid Schauss
• Subject Area: Nephrology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 386793560

Central project CP2 coordinates the generation and standardized analysis of mouse models within the CRU329. B. Zevnik, head of the in vivo research facility (ivRF) at CECAD, will support each individual research project in the generation of transgenic and genome edited mouse lines and the development of novel in vivo models to study podocyte biology and pathophysiology. These genetic approaches include the combination of different DNA recombinases, multi-cistronic knock-in strategies with 2A-peptides, and CRISPR/Cas technologies with the aim of a podocyte-specific manipulation of gene expression, of mimicking human genetic diseases as well as of expression of additional transgenes - all in a time and cost-efficient manner. This unique in vivo pipeline has contributed significantly to the success of the first funding period of the CRU329 (Aim 1). For the phenotypic characterization of the animal models modern imaging technologies are instrumental (Aim 2). Both light microscopic methods and electron microscopy are used. Both are provided by A. Schauss, head of the CECAD imaging facility, and were already of greatest importance for the success of the CRU329 in the first funding period. M. Höhne with his proven expertise in the field of different light microscopy platforms oversees and bundles the administrative organization of image acquisition and analysis. Together with A. Schauss, M. Höhne coordinated the establishment of an OMERO platform for CRU329, which enables the sharing and interactive exchange of data in the consortium. Among other features, a digital nephropathology platform has been established together with C. Schell (Institute of Clinical Pathology, University of Freiburg), which enables annotation and digital review of kidney biopsies both from animal models and from patients. Another goal of CP2 (Aim 3) is the automated analysis of kidney sections from mouse tissue as well as from human kidney biopsies. For this purpose, K. Bozek (CMMC) will perform a mathematical modeling using computer-based machine learning algorithms.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 329: Disease pathways in podocyte injury – from molecular mechanisms to individualized treatment options
• Co-Investigators: Dr. Martin Höhne; Professor Dr. Christoph B. Schell