Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese

摘要

Divalent metal-ion transporter-1 (DMT1) is a widely expressed iron-preferring membrane-transport protein that serves a critical role in erythroid iron utilization. We have investigated its role in intestinal metal absorption by studying a mouse model lacking intestinal DMT1 (i.e., DMT1~(int/int)). DMT1~(int/int) mice exhibited a profound hypochromic-microcytic anemia, splenomegaly, and cardiomegaly. That the anemia was due to iron deficiency was demonstrated by the following observations in DMT1~(int/int) mice: i) blood iron and tissue nonheme-iron stores were depleted; 2) mRNA expression of liver hepcidin (Hamp1) was depressed; and 3) intraperitoneal iron injection corrected the anemia, and reversed the changes in blood iron, nonheme-iron stores, and hepcidin expression levels. We observed decreased total iron content in multiple tissues from DMT1~(int/int) mice compared with DMT1~(+/+) mice but no meaningful change in copper, manganese, or zinc. DMT1~(int/int) mice absorbed ~64Cu and ~54Mn from an intragastric dose to the same extent as did DMT1~(+/+) mice but the absorption of ~59Fe was virtually abolished in DMT1~(int/int) mice. This study reveals a critical function for DMT1 in intestinal nonheme-iron absorption for normal growth and development. Further, this work demonstrates that intestinal DMT1 is not required for the intestinal transport of copper, manganese, or zinc.