Intestinal iron uptake determined by divalent metal transporter is enhanced in HFE-deficient mice with hemochromatosis

Gastroenterology. 2001 May;120(6):1420-9. doi: 10.1053/gast.2001.24050.


Background & aims: Overexpression of duodenal divalent metal transporter (DMT1) messenger RNA occurs in hemochromatosis and HFE-knockout mice, suggesting that DMT1 mediates enhanced absorption of iron; however, increased expression of functional DMT1 protein has yet to be substantiated. We examined the role of DMT1 and the mucosal iron uptake defect in HFE-knockout mice.

Methods: Unidirectional iron uptake of 59Fe by small intestinal mucosa in vitro was compared between matched pairs of HFE-knockout and wild-type mice. DMT1-specific antibodies were used to block iron transport and to quantify duodenal protein expression.

Results: Ferrous iron uptake at 3.5-450 micromol/L was greatly enhanced in HFE-knockouts compared with wild-type, the apparent V(max) for Fe2+ transport being doubled (P < 0.01). Supplied as Fe3+, uptake was only enhanced in HFE-knockouts at < or =18 micromol/L, when the iron was almost completely converted to Fe2+ by mucosal ferrireductases. DMT1 antibody reduced the apparent Vmax for mucosal Fe2+ transport in HFE-knockouts to below wild-type control values (P < 0.02); immunoreactive mucosal DMT1 protein was increased nearly 2-fold in HFE-knockouts (P < 0.01).

Conclusions: Disruption of the HFE gene up-regulates functional DMT1 transporters and enhances uptake of ferrous iron by this mechanism; DMT1 also mediates increased uptake after reduction of ferric iron presented at physiological concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / physiology*
  • Cation Transport Proteins*
  • Female
  • HLA Antigens / genetics*
  • Hemochromatosis / metabolism*
  • Hemochromatosis / therapy
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I / genetics*
  • Hydrogen-Ion Concentration
  • Intestinal Mucosa / metabolism*
  • Iron / metabolism*
  • Iron-Binding Proteins*
  • Male
  • Membrane Proteins*
  • Mice
  • Mice, Knockout


  • Carrier Proteins
  • Cation Transport Proteins
  • HLA Antigens
  • Hemochromatosis Protein
  • Hfe protein, mouse
  • Histocompatibility Antigens Class I
  • Iron-Binding Proteins
  • Membrane Proteins
  • solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
  • Iron