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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.

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