Disease Models

The development and application of in vitro, ex vivo and in vivo models of rare kidney diseases is a major focus of the Consortium. The partners will share their unique methodological expertise in the functional analysis of mutant proteins, antigens and auto-antibodies, promoter regulation, as well as sophisticated glomerular, tubular, endothelial and renal progenitor cell culture models. In the quest to generate and use patient-derived inducible pluripotent stem cells in organoid culture systems, partners INSERM Institute of Biology Valrose and University of Oulu will team up with Dr. Christine Mummery (Leiden University) in a Network of Competence in Stem Cell Technology. Dr. Mummery is highly renowned for her ground-breaking work in stem cell technology. She has created almost 30 human and mouse control and mutant iPSC lines from skin and blood cells.

For cell-based high-throughput compound screening the partners will collaborate with Biophenics, an Automated Imaging Platform for High Content Screening and Phenotyping Fingerprinting well established at the Institut Curie (Paris). Lower vertebrate models are a relatively recent field of research with great potential regarding therapeutic target validation and high-throughput drug screening for therapeutic targets. The Consortium will make intense efforts to utilize the current expertise in the field in order to develop zebrafish and Xenopus (frog) models of inherited kidney diseases and derive systems that will allow efficient large-scale drug screening. For this purpose, a Network of Competence in Lower Vertebrate Research will be implemented, which will include the leading international zebrafish experts Iain Drummond (Boston) and Rachel Giles (Utrecht), Urban Liebel from the Zebrafish imaging and screening unit at the Karlsruhe Institute of Technology, and André Brändli (Ludwig-Maximilians-Universität Munich), a leading expert in Xenopus pronephros development and function. These experts will guide the Consortium in developing appropriate lower vertrebrate models of glomerular, tubular, complement and global renal developmental disorders. The consortium as a whole has present access to more than 30 genetically modified mouse models of human kidney diseases. Besides knockout models, the investigators have established several constitutive and inducible knock-in models mimicking the human disease condition.