The primary role of Core C (the Animal Core) is to provide the appropriate animals required by the individual projects within the Program Project. The Animal Core will serve three basic support functions. First, the Animal Core will be responsible for maintaining the ETe-receptor deficient rat colony required by Projects 1 and 2, the cell-specific knockout mice required by Projects 3 and 4, and the appropriate control colonies. Second, the Animal Core will be responsible for generating the collecting duct-specific double knockout mice used in Project 3. Third, the Animal Core will provide for the continuous measurement of mean arterial pressure, heart rate and physical activity using the Data Sciences telemetry systems in all required rat and mouse studies in Projects 1, 2, and 3.
Aim 1 is to provide the ETe-receptor deficient rats and the collecting duct NOSI knockout mice. This will include setting up the appropriate breeding pairs, collecting tissue and coordinating with Core B for genotyping, and ensuring that a sufficient number of animals are available for the individual projects. These animal models will be provided by the section of the Core located at the Medical College of Georgia.
Aim 2 is to provide the collecting duct ET-1, ETA and ETB receptor knockout mice. This will include setting up the appropriate breeding pairs, genotyping, and coordinating with the Medical College of Georgia and the University of Texas Health Science Center to provide sufficient numbers of animals for the individual projects. These mice will be provided by the University of Utah.
Aim 3 is to provide the collecting duct N0S1/ET-1 double knockout mice. This will include breeding floxed NOSI, floxed ET-1 and aquaporin-2 (AQP2)-Cre mice. These are being developed for Project 3.
Aim 4 is to provide continuous measurement of mean arterial pressure, heart rate and physical activity in mice and rats at the Medical College of Georgia. This will include scheduling, and providing materials, surgery, and daily monitoring throughout the study for the individual projects. The Animal Core has been structured to provide the highest degree of quality control and allow for consistency in animal models across all of the individual projects of the Program Project. This will involve very closely coordinated efforts and sharing of expertise between the groups at the University of Utah and the Medical College of Georgia.
The Program Project focuses on elucidating mechanisms by which the kidney controls sodium excretion, and therefore, has direct relevance to the serious health problem of salt-dependent hypertension and kidney disease. The Animal Core will be critical in providing quality control for all animal studies and ensuring that the appropriate animal models are available to the individual projects in sufficient quantities.
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