Figure 6. Nephron formation defects in Foxd1-Phd2^−/−-Phd3^−/− mice require HIF-2α.

(A) Shown are representative images of Periodic acid-Schiff (PAS)-stained kidney sections (top) and CD31-and ACTA2 IHC staining (middle and lower panels) for Cre⁻ control (Foxd1^+/+ Phd2^fl/fl Phd3^fl/fl Hif2a^fl/fl), Foxd1-Phd2^−/−-Phd3^−/−-Hif1a^−/− and Foxd1-Phd2^−/−-Phd3^−/−-Hif2a^−/− mutant kidneys at P14. Asterisks depict glomeruli and arrows indicate renal tubules with PAS-positive brush borders. Scale bars represent 50μm. (B) mRNA expression levels of Epo, nephron-segment-specific and vascular markers in whole kidney homogenates from Foxd1-Phd2^−/−-Phd3^−/−-Hif1a^−/− and Foxd1-Phd2^−/−-Phd3^−/−-Hif2a^−/− compared to Cre⁻ controls (n=4 for Foxd1^+/+ Phd2^fl/fl Phd3^fl/fl Hif2a^fl/fl control mice; n=3 for Foxd1-Phd2^−/−-Phd3^−/−-Hif1a^−/− mutants; n=5 each for Foxd1-Phd2^−/−-Phd3^−/−-Hif2a^−/− mice). Data are represented as mean ± SEM; 2-tailed Student’s t-test; *p<0.05, **p<0.01 and ***p<0.001. Acta 2, α-smooth muscle actin; Aqp1, aquaporin 1; Aqp2, aquaporin 2; NaPi2a, sodium-phosphate co-transporter-2a; Ncc NaCl co-transporter; Nkcc2, Na-K-2Cl co-transporter Scnn1a, sodium channel epithelial 1 alpha subunit; Trpv5, transient receptor potential cation channel subfamily V member 5.