Erythrocytosis is mainly caused by extramedullary erythropoiesis in the spleen. (A-B) Representative sections of WT and cKO P2 spleens (H&E) show an extensive structural loss and an augmentation of nucleated cells in erythrocytotic cKO P2 mice. (C) Spleen weight of WT and cKO P2 mice (n = 10-16). (D-G) Representative FACS staining profiles of (D and E) megakaryocyte-erythrocyte progenitors (MEP; n = 6) and (F-G) erythroblasts (EB; n = 7) in BM and spleen of WT and cKO P2 showing that the overproduction of RBCs is mainly executed in the spleen. Scale bars represent 500 μm. All data are mean ± SEM (*P < .05, ***P < .001).