Diabetic Nephropathy Mouse Model Study

Experiments were conducted in male D2.B6-Ins2^Akita/MatbJ and their wild-type littermate mice (Dilute Brown Agouti [DBA]/2J background; The Jackson Laboratory, stock number 007562) starting at 5 weeks of age (2 weeks of diabetes) until 14 weeks of age (11 weeks of diabetes). Ins2^Akita mice, recommended by the Animal Models of Diabetes Complications Consortium as an optimal model of DN (18 (link),19 (link)), developed hyperglycemia at 3 weeks of age. Additional experiments were conducted in male 6-week-old DBA/2J mice (The Jackson Laboratory, stock number 000671) and in male arginase-2–deficient (Arg2^−/−) mice on C57BL/6J background (provided by B. Lee, Baylor College of Medicine, Houston, TX) using multiple low doses of vehicle (lactated Ringer’s solution) or STZ (Sigma, St. Louis, MO; 50 mg/kg body wt dissolved in lactated Ringer’s solution) via intraperitoneal injection. All animal studies were approved by the Penn State University College of Medicine Institutional Animal Care and Use Committee.