Tmprss6^−/− mice sense anemia but do not respond to EPO. C57BL/6 WT or Tmprss6 KO mice were non-injected or injected with EPO (5 to 8 mice per group) and were addressed 15 hours later for (A) liver non-heme iron content; (B) liver Hamp mRNA expression; (C) serum hepcidin levels; (D) serum Epo levels; (E) BM Erfe mRNA expression; and (F) liver pSmad-5 relative to total Smad5 protein. Results are expressed as mean ± SD and compared by Student t tests (A,D) or by ANOVA followed by Sidak’s multiple comparison tests. ****P < .0001; ***P < .001; **P < .01; *P < .05. Point estimates of the fold changes in gene expression (2^−ΔΔCt) are shown on the graphs.