Mice were exposed to either non-UO sham-operation or left UO, which continued for 24 hours, and then was released. At different time points (0 d, 2 d, 4 d, 7 d) after release of UO, animals were subjected to right nephrectomy, followed by IR (25 min of left renal ischemia and 24 h of reperfusion) or non-IR sham operation. A, concentrations of serum creatinine 24 h after the initiation of reperfusion. B, representative renal PAS-stained sections from mice of UO 2 d group and their non-UO controls (original magnification ×200). Sections from HIF-1α−/−, HIF-2α−/− and DKO mice in non-IR groups had no positive manifestations (similar to those of WT non-IR mice) and were not shown. C, abnormalities based on PAS-stained sections was graded by a semiquantitative histomorphological scoring system from 0 to 4. All mice in non-IR groups had no tubular damage (histomorphological score: 0, data not shown). Data were expressed as mean ± SD from 6–8 animals per genotype. *, p<0.05 versus WT mice that were treated with the same procedures.