N lobe–bound iron enhances erythropoietin responsiveness. (A) Complete blood cell parameters from mice treated with 3000 IU/kg per day of recombinant human Epo demonstrated increased RBC counts in WT and Tf^C-bl/C-bl mice but not in Tf^N-bl/N-bl mice treated with Epo relative to controls (for saline-treated mice, n = 8-12 mice per sex for WT and n = 3-6 mice per sex for mutant mice; for Epo-treated mice, n = 6-9 mice per sex for WT and n = 4-5 mice per sex for mutant mice). (B) In response to Epo treatment, the change in RBCs, as measured by subtracting the average RBC count of respective saline-treated controls, was increased in Tf^C-bl/C-bl mice compared with WT and Tf^N-bl/N-bl mice (n = 4-6 mice per sex for each strain). (C) Hb concentrations in mice treated with Epo relative to controls showed significant increases in Hb concentration in WT and Tf^C-bl/C-bl mice (for saline-treated mice, n = 8 mice per sex for WT and n = 3-6 mice per sex for mutant mice; for Epo-treated mice, n = 6-7 mice per sex for WT and n = 4-7 mice per sex for mutant mice). (D) In response to Epo treatment, the change in Hb, as measured by subtracting the average Hb of respective saline-treated controls, was greater in WT and Tf^C-bl/C-bl mice than in Tf^N-bl/N-bl mice, with a more substantial increase in the Tf^C-bl/C-bl mice (n = 6-10 mice per sex for WT and n = 3-5 mice per sex for mutant mice). Data are presented as Tukey box and whisker plots. Statistical significance was analyzed by 1-way ANOVA. *P ≤ .05, **P ≤ .01, ***P ≤ .001, ****P ≤ .0001.