Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese

Am J Physiol Gastrointest Liver Physiol. 2015 Oct 15;309(8):G635-47. doi: 10.1152/ajpgi.00160.2015. Epub 2015 Aug 20.


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.

Keywords: SLC11A2; copper absorption; iron deficiency; iron-deficiency anemia; iron-refractive iron-deficiency anemia; manganese absorption; zinc metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anemia, Hypochromic / genetics
  • Anemia, Hypochromic / pathology
  • Animals
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Copper / metabolism*
  • Copper Transporter 1
  • Gene Expression Regulation / physiology
  • Homeostasis / physiology
  • Intestinal Absorption / physiology*
  • Iron / metabolism*
  • Manganese / metabolism*
  • Mice
  • Mice, Knockout
  • Zinc / metabolism


  • Cation Transport Proteins
  • Copper Transporter 1
  • Slc31a1 protein, mouse
  • solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
  • Manganese
  • Copper
  • Iron
  • Zinc