title: Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese.
abstract: Divalent metal-ion transporter-1 (DMT1) is a widely expressed iron-preferring membrane-transport protein that serves a critical role in erythroid iron utilization. We have investigated its role in intestinal metal absorption by studying a mouse model lacking intestinal DMT1 (i.e., DMT1(int/int)). DMT1(int/int) mice exhibited a profound hypochromic-microcytic anemia, splenomegaly, and cardiomegaly. That the anemia was due to iron deficiency was demonstrated by the following observations in DMT1(int/int) mice: 1) blood iron and tissue nonheme-iron stores were depleted; 2) mRNA expression of liver hepcidin (Hamp1) was depressed; and 3) intraperitoneal iron injection corrected the anemia, and reversed the changes in blood iron, nonheme-iron stores, and hepcidin expression levels. We observed decreased total iron content in multiple tissues from DMT1(int/int) mice compared with DMT1(+/+) mice but no meaningful change in copper, manganese, or zinc. DMT1(int/int) mice absorbed (64)Cu and (54)Mn from an intragastric dose to the same extent as did DMT1(+/+) mice but the absorption of (59)Fe was virtually abolished in DMT1(int/int) mice. This study reveals a critical function for DMT1 in intestinal nonheme-iron absorption for normal growth and development. Further, this work demonstrates that intestinal DMT1 is not required for the intestinal transport of copper, manganese, or zinc.
authors: Department of Molecular & Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio; Systems Biology & Physiology Program, University of Cincinnati College of Medicine, Cincinnati, Ohio;
authors: Ali
authors: A
authors: Shawki
authors: Department of Molecular & Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio;
authors: Sarah R
authors: SR
authors: Anthony
authors: Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina;
authors: Yasuhiro
authors: Y
authors: Nose
authors: Department of Molecular & Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio; Systems Biology & Physiology Program, University of Cincinnati College of Medicine, Cincinnati, Ohio;
authors: Melinda A
authors: MA
authors: Engevik
authors: Department of Molecular & Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio;
authors: Eric J
authors: EJ
authors: Niespodzany
authors: Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina;
authors: Tomasa
authors: T
authors: Barrientos
authors: Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina; Department of Medical Biochemistry & Microbiology, Uppsala University, Uppsala, Sweden; and.
authors: Helena
authors: H
authors: Öhrvik
authors: Department of Molecular & Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio; Systems Biology & Physiology Program, University of Cincinnati College of Medicine, Cincinnati, Ohio;
authors: Roger T
authors: RT
authors: Worrell
authors: Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina; Department of Biochemistry, Duke University Medical Center, Durham, North Carolina.
authors: Dennis J
authors: DJ
authors: Thiele
authors: Department of Molecular & Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio; Systems Biology & Physiology Program, University of Cincinnati College of Medicine, Cincinnati, Ohio; bryan.mackenzie@uc.edu.
authors: Bryan
authors: http://orcid.org/0000-0002-9661-8838
authors: B
authors: Mackenzie
mesh_terms: D000747:Anemia, Hypochromic / Q000235:genetics / Q000473:pathology; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D005786:Gene Expression Regulation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D007408:Intestinal Absorption / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015032:Zinc / Q000378:metabolism; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000079923:Copper Transporter 1; D007501:Iron; D008345:Manganese; D015032:Zinc; D000099236:Solute Carrier Family 11, Member 2; C490077:Slc31a1 protein, mouse
keywords: SLC11A2; copper absorption; iron deficiency; iron-deficiency anemia; iron-refractive iron-deficiency anemia; manganese absorption; zinc metabolism