Loss of intestinal PCBP1 disrupts systemic iron homeostasis, causing liver iron loading or anemia. (A) Elevated plasma iron in PCBP1^ΔIEC mice. Nonheme iron levels were measured in plasma of WT and PCBP1^ΔIEC mice that were fed 5 ppm, 50 ppm, and 1000 ppm iron diets for 1 month. (B) Iron accumulation in the livers of PCBP1^ΔIEC mice that were fed a high-iron diet. Nonheme iron measured in liver tissue from WT and PCBP1^ΔIEC mice from panel A. (C) Iron accumulation in bone marrow of PCBP1^ΔIEC mice. Nonheme iron measured in bone marrow of mice that were fed a tamoxifen diet for 1 month after weaning. (D) More severe anemia in PCBP1^ΔIEC vs WT mice on a low-iron diet. Complete blood counts were obtained on mice fed a 5 ppm iron diet for 1 month. Horizontal line indicates values from WT mice that were fed a 50 ppm diet. (E) Impaired maturation of erythroid precursors in PCBP1^ΔIEC mice that were fed a low-iron diet. Erythroid precursors of mice that were fed a 5 ppm iron diet analyzed by flow cytometry. Dot plots and gating strategies shown on the left, subgroup quantification shown on the right. Refer to supplemental Figure 4. (F) Increased expression of erythroid regulators ERFE and EPO in PCBP1^ΔIEC mice that were fed a low-iron diet. Bone marrow and kidney mRNA was prepared from mice treated as in panel D and analyzed by qPCR. (G) Excess absorption of oral iron through intestine into the circulation in PCBP1^ΔIEC mice. Mice were administered ⁵⁷FeSO₄ solution through oral gavage. IEC, plasma, and liver samples were collected at 1 hour and ⁵⁷Fe levels were measured by ICP-MS. (H) Activation of Nrf2-controlled, oxidative stress response genes in livers of PCBP1^ΔIEC mice. Mice were fed defined-iron diets for 1 month and mRNA levels of oxidative stress genes NQO1, SLC3a2, and MT1 were measured in liver tissue by qPCR. Refer to supplemental Figure 3.