Endothelial SENP1 Knockout Diabetic Mouse Model

Vascular endothelial cell (EC)-specific deletion of SENP1 (SENP1-ECKO), which was generated by mating SENP1^lox/lox with VE-cadherin-Cre mice^{24 (link),25 (link)} followed by breeding to C57BL/6 background. The deletion of SENP1 in SENP1-ECKO was verified by qRT-PCR using primers amplifying exons 5–6 and specific Cre. SENP1^lox/lox mice were used as controls. We used a standard protocol of STZ injections to induce type I diabetes (T1DM) in C57BL/6 mice. Briefly, C57BL/6 mice at 8 weeks of age mice were injected intraperitoneally with 45 mg/kg STZ or PBS daily for 4 days. Blood glucose concentrations in non-fasting mice were measured 14–16 days after the first injection by an electronic glucometer (Abbott Diabetes Care, Alameda, CA). Blood glucose levels in STZ-treated mice were 350 ± 40 mg/dL (higher than 250 mg/dL were considered diabetic). PBS-treated mice were used as controls for further experiments. Mice were cared for in accordance with National Institutes of Health guidelines, and all procedures were approved by the Yale University Animal Care and Use Committee.