Conditional deficient PHD2 mice display severe HIF-2α–induced erythrocytosis. (A) Compared with WT mice, cKO P2 show profound redness of the snout and paws. (B) Body weight of WT and cKO P2 mice was measured on a weekly basis until adulthood. No significant difference was observed after week 8 (n = 5-11). (C) Percentage of red blood cell volume per blood volume (HCT-hct) from mice was measured every 2 weeks until adulthood, displaying highly significant differences from week 4 after birth (n = 5-10). (D) HCTs in cKO P2/H1 remained as high as in cKO P2 mice whereas cKO P2/H2 mice showed even slightly but significantly lower HCTs than WT (n = 6-15). (E-F) RBC count (n = 7-32) and hemoglobin (n = 6-22) concentration in freshly isolated blood samples demonstrate that HIF-2α but not HIF-1α induces erythrocytosis because of loss of PHD2. All data are mean ± SEM (*P < .05, **P < .01, ***P < .001).