Erfe-deficient mice compensate for hepcidin dysregulation by prolonged erythropoietic stimulation. (A) High EPO concentrations were sustained at 21 days in Erfe-deficient mice (black bars, mean EPO concentration = 3111 pg/mL) compared with WT mice (white bars, mean EPO concentration = 1303 pg/mL, P = .001, shown previously in Figure 1A). Erfe^−/− mice had a higher RBC count (B) and spleen index (C) on day 28 than WT mice (spleen index = spleen weight in mg/body weight in g). (D) Nonheme spleen iron content peaked earlier in WT than in Erfe^−/− mice. (A) Serum EPO levels are shown as means ± SEM and were compared for each time point to values for control mice at t = 0 (n = 6-7 per time point) by 2-tailed Student t test. Data shown for RBC (B), spleen index (C), and total spleen iron (D) are means ± SEM and were compared between WT and Erfe^−/− mice for each time point (n = 6-7 per time point) by 2-tailed Student t test (***P < .001, **P < .01, *P < .05). WT data shown in panel A are identical to those from Figure 1A.