Global loss of Tet1 causes an altered response to iron overload. (A) Serum iron levels and transferrin saturation (TS) were measured in HID-fed control (Tet1^+/+) and Tet1^−/− mice (n = 10-12 mice per group). (B) Nonheme iron concentration was measured in the indicated tissues of HID-fed Tet1^+/+ and Tet1^−/− mice (n = 8-12 mice per group). (C) Perls’ Prussian blue staining and quantification of iron measured in duodenum, spleen, and liver sections obtained from HID-fed Tet1^+/+ and Tet1^−/− mice (n = 4 mice per group). (D) RT-PCR analysis of hepatic Hamp1 mRNA in SID- and HID-fed Tet1^+/+ and Tet1^−/− mice (n = 6-7 mice per group). (E) RT-PCR analysis of Fpn, Dmt1, Tfr1, and Fth mRNA in the liver, enterocytes, and spleen of HID-fed Tet1^+/+ and Tet1^−/− mice (n = 6-8 mice per group). (F) FPN immunohistochemistry and quantification of duodenum, spleen, and liver sections obtained from HID-fed Tet1^+/+ and Tet1^−/− mice (n = 4 mice per group). Scale bars, 100 μm (C,F). *P < .05 and **P < .01 (Student t test).