Minihepcidin peptide ameliorated hypoxia in animals affected by non–transfusion-dependent thalassemia.Hbb^th3/+ mice were crossed with the hypoxia reporter mouse ODD-Luc and treated with M004 (2.625 mg/kg) twice a week for 6 weeks. As expected, minihepcidin administration increased RBC numbers (A) and Hb level (B) and reduced reticulocyte count (C) and splenomegaly (D). Improved erythropoietic efficiency was confirmed by flow cytometry analysis of erythroid precursors (as shown in the CD44-FSC [forward scatter] plots) (E). Reduction in hypoxia was evaluated by in vivo imaging. Reduction in luminescence was detected in the abdomen of animals receiving minihepcidin compared with the vehicle-treated one, indicating reduction in hypoxia (F). Results are presented as mean ± SD; *P < .05, 2-tailed Mann-Whitney U test. WT data are displayed as a reference guide but are not included in the between-group test comparisons.