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