Figure 3.

Loss of Prolyl Hydroxylase Domain Enzymes Does Not Initiate Renal Cyst Formation

(A) H&E staining of sections of kidneys from wild-type control, Phd1^−/−Phd3^−/− and Phd1^−/−Phd2^−/−Phd3^−/− mice at 17 and 24 weeks of age confirming the absence of renal cysts; scale bar = 100 μm. Kidneys from wild-type, and Phd1^−/−Phd3^−/− double knockout mice show no abnormal pathology. Kidneys from Phd1^−/−Phd2^−/−Phd3^−/− mice have subtle vacuolization, but show no evidence of either tubular dilation or cyst formation.

(B) IHC for Hif-1α was performed on kidney sections from 24-week-old control, Phd1^−/−Phd3^−/− and Phd1^−/−Phd2^−/−Phd3^−/− mice. Hif-1α staining (highlighted in insert) is observed only in the Phd1^−/−Phd2^−/− Phd3^−/− mice in the nuclei of cells lining the renal tubules and not in the interstitium; scale bar = 100 μm.

(C) Immunoblot of lysates of kidneys from control, Phd1^−/−Phd3^−/− and Phd1^−/−Phd2^−/−Phd3^−/− mice for Hif-1α showing stabilization of Hif-1α in only the kidneys of the Phd1^−/−Phd2^−/−Phd3^−/− mice. Protein loading is indicated by β-actin.