Genetically engineered mice required to study oxidative stress in this Program Project Grant will be bredand maintained by Core B. Oxidative stress is due to excess reactive oxygen species generated byNADPH oxidase (NOX) or reduced function of superoxide dismutases (SOD), the major antioxidantdefense. The Core will maintain two current strains of C57/BI6 background knockout mice: theextracellular superoxide dismutase (EC-SOD) knockout and the dopamine, type 5 receptor (D5R). Inaddition, two colonies of knockout mice will be developed: intracellular superoxide dismutase (IC-SOD)knockout mice and mice heterozygous for manganese superoxide dismutase (Mn-SOD). The Mn-SODknockout is lethal. Core B will use heterozygous breeders to produce both wild type and knockouts in asingle litter. Adult male knockout mice will be used for all experiments and the control group will be adultmale wild type littermates. In addition, Core B will measure conscious mean arterial blood pressure, byradiotelemetry and renal blood flow, by ultrasonic flow probes in all mouse models used in the Program.This will include additional mice treated with small interfering RNA to knock down p22phox, the criticalsubunit for NOX and for fibroblast growth factor transgenic mice. Function in these mice will be measuredafter treatment with vehicle or angiotensin II to induce oxidative stress. Additional mice in each group willbe used to measure renal function, including glomerular filtration rate, renal plasma and blood flow, renalvascular resistance, urine flow, oxygen consumption and blood gas levels under anesthesia. Core B willalso measure a series of hormones, enzymes and end products that are related to oxidative stress effectsin the kidney. Core B will also provide technical assistance to each project on animal issues, includingmouse physiology and data analysis.
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