In wild-type mice, 3 prolyl hydroxylase domain proteins (PHD1, PHD2, and PHD3) that are critical for HIF-α degradation are present. HIF-α levels are kept at low levels and erythropoiesis is normal. When the animals are deficient for PHD2, HIF-1α is up-regulated and erythropoiesis is stimulated. In contrast to PHD2-deficient mice, PHD1 and PHD3 double-knockout mice show activation of HIF-2α, which also leads to erythrocytosis.