Role of the iron‐import protein DMT1 (Divalent Metal Transporter 1) in liver iron uptake

DMT1 is required for intestinal iron absorption and the uptake of iron by developing erythroid cells. Here we used hepatocyte‐specific DMT1 knockout mice ( Dmt1 liv/liv ) to examine the role of DMT1 in the liver. Dmt1 liv/liv mice were crossed with models of genetic iron overload, i.e., Hfe − / − and hypotransferrinemic ( Hpx ) mice, to determine the role of DMT1 in hepatic iron accumulation. We found that Dmt1 liv/liv mice had normal hepatic non‐heme iron concentrations and that the double‐mutant Dmt1 liv/liv :Hfe − / − and Dmt1 liv/liv :Hpx mice accumulated similar amounts of hepatic iron as did their respective Hfe − / − and Hpx controls. To determine if hepatocyte DMT1 is required for the uptake of non‐transferrrin‐bound iron (NTBI) and the assimilation of iron from transferrin, we injected 59 Fe‐labeled NTBI or transferrin into Dmt1 liv/liv mice and measured hepatic 59 Fe uptake. We found that Dmt1 liv/liv mice efficiently took up NTBI, but had a 40% reduction in the assimilation of iron from transferrin. These data indicate that DMT1 is not required for hepatic iron accumulation under normal and iron overload conditions, but it is required for the efficient assimilation of iron from transferrin. Funded by NIH. Grant Funding Source : NIH