Ablation of Erfe in thalassemic mice decreases iron overload. Liver (A) and spleen (B) nonheme iron content was measured in WT, Th3/+, Erfe^+/−, Th3/+, and Erfe^−/−, Th3/+ at 3, 6, and 12 weeks of age. Mice with thalassemic trait mice had higher liver iron content at all ages compared with WT mice. Erfe-deficient mice on a thalassemic background (Erfe^−/−, Th3/+) had reduced liver (A) and spleen (B) iron content compared with Th3/+ mice at 6 and 12 weeks of age. No difference in liver and spleen iron content was observed between the genotypes in 3-week-old animals, and the spleen iron content was not detectable in most of the mice at the age of 3 weeks. Data shown are means ± SEM and were compared for each age between Erfe^−/−, Th3/+ or Erfe^+/−, Th3/+ mice and Th3/+ mice (n = 9-36 per group) by 2-tailed Student t-test. ***P < .001, **P < .01, *P < .05. WT mice had significantly lower liver and spleen iron content compared with all the thalassemic mice (#P < .05 or less). Note that the data in A for 6-week-old mice were previously shown in Figure 7E of Kautz et al.¹²