Vanderbilt O'Brien Kidney Center-Core A Physiology-Pathiophysiology Core

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ABSTRACT The Phenotyping and Pathophysiology Core is designed to address the need for effective phenotyping of kidney function in mouse models of selective gene overexpression or deletion. In addition, this Core is designed to provide experimental mouse models of acute or progressive renal injury to assess potential therapeutic interventions. This Core also helps investigators who may have developed genetic mouse models or potential therapeutic interventions but do not have the expertise and/or infrastructure required to design and carry out appropriate kidney phenotyping studies or studies investigating mouse models of kidney injury. In this proposal, we propose five distinct subcores that will offer and/or develop methodologies to define the pathogenesis of kidney disease and design therapeutic interventions. The Phenotyping Subcore will provide a battery of well-established invasive and non-invasive tests of kidney function. The Injury Model Subcore will provide investigators cost-effective testing of potential pharmaceutical or immunologic therapy strategies in appropriate mouse models of acute or progressive kidney injury. In addition, this subcore will provide murine models for screening of potential kidney side effects of drugs. This subcore provides a wide variety of experimental models of mouse kidney injury that offer consistent and reproducible results. Some of the mouse models available have been developed by the Center investigators. The Metabolism and Bioenergetics Subcore will offer direct measurements of kidney tissue partial oxygen consumption and will develop methodology for the measurements of whole kidney oxygen consumption based on kidney blood flow and measurements of arterial and renal venous partial oxygen. Furthermore this subcore will provide expertise in metabolic flux analysis, glucose uptake and quantification of various metabolites in kidney tissues using mass spectrometry methods. The Mouse Kidney Imaging Subcore will provide established non-invasive imaging techniques for the assessments of mouse renal diseases and will provide methods and further optimize novel methods for the noninvasive characterization of renal microstructure and function in mice. The CRISPR/cas9 Subcore will provide guidance for the design, construction, and generation of a CRISPR mouse. In summary, the Phenotyping and Pathophysiology Core provides a broad range of services that aid researchers interested in utilizing murine models for kidney-related research. The structure of this Core is unique in that it performs a variety of kidney functions, non-invasive quantitative kidney images analysis, and experimental platforms for the testing of drugs and interventions. Importantly, this Core performs all these services in house and directly oversees these studies. We have been very successful in providing these services not only to the local scientific community interested in kidney research, but also in serving as a national and international resource.