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

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 k nown to be important for the uptake of dietary non-heme iron from the gut l umen. The expression and subcellular localization of DMT1 protein in 3 mous e models of iron over-load were examined: hypotransferrinemic (Trf(hpx)) mi ce, Hfe knockout mice, and B2m knockout mice. Interestingly, in Trfhpx homo zygotes, DMT1 expression was strongly induced in the villus brush border wh en compared to control animals. This suggests that DMT1 expression is incre ased in response to iron deficiency in the erythron, even in the setting of systemic iron overload. In contrast, no increase was seen in DMT1 expressi on in animals with iron overload resembling human hemochromatosis. Therefor e, it does not appear that changes in DMT1 levels are primarily responsible for iron loading in hemochromatosis.