Expression of the DMT1 (NRAMP2/DCT1) iron transporter in mice with genetic iron overload disorders

Blood. 2001 Feb 15;97(4):1138-40. doi: 10.1182/blood.v97.4.1138.

Abstract

Iron overload is highly prevalent, but its molecular pathogenesis is poorly understood. Recently, DMT1 was shown to be a major apical iron transporter in absorptive cells of the duodenum. In vivo, it is the only transporter known to be important for the uptake of dietary non-heme iron from the gut lumen. The expression and subcellular localization of DMT1 protein in 3 mouse models of iron overload were examined: hypotransferrinemic (Trf(hpx)) mice, Hfe knockout mice, and B2m knockout mice. Interestingly, in Trf(hpx) homozygotes, DMT1 expression was strongly induced in the villus brush border when compared to control animals. This suggests that DMT1 expression is increased in response to iron deficiency in the erythron, even in the setting of systemic iron overload. In contrast, no increase was seen in DMT1 expression in animals with iron overload resembling human hemochromatosis. Therefore, it does not appear that changes in DMT1 levels are primarily responsible for iron loading in hemochromatosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • CHO Cells
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Cation Transport Proteins*
  • Cricetinae
  • Cricetulus
  • Disease Models, Animal
  • Duodenum / metabolism
  • Gene Expression Regulation*
  • Genotype
  • HLA Antigens / genetics
  • Hemochromatosis / genetics
  • Hemochromatosis / metabolism
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I / genetics
  • Intestinal Absorption
  • Iron / pharmacokinetics
  • Iron Overload / genetics*
  • Iron Overload / metabolism
  • Iron-Binding Proteins*
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Transferrin / deficiency
  • Transferrin / genetics
  • beta 2-Microglobulin / deficiency
  • beta 2-Microglobulin / genetics

Substances

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