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Blood, 15 February 2001, Vol. 97, No. 4, pp. 1138-1140

BRIEF REPORT

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

François Canonne-Hergaux, Joanne E. Levy, Mark D. Fleming, Lynne K. Montross, Nancy C. Andrews, and Philippe Gros

From the Department of Biochemistry, McGill University, Montreal, Canada; Division of Hematology/Oncology, Children's Hospital; Howard Hughes Medical Institute; Division of Hematology, Brigham and Women's Hospital; Department of Pathology, Children's Hospital; and Department of Pediatrics, Harvard Medical School, Boston, MA.

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 (Trfhpx) mice, Hfe knockout mice, and B2m knockout mice. Interestingly, in Trfhpx 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.

© 2001 by The American Society of Hematology.
 

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