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

A Shawki, SR Anthony, Y Nose… - American Journal …, 2015 - journals.physiology.org
A Shawki, SR Anthony, Y Nose, MA Engevik, EJ Niespodzany, T Barrientos, H Öhrvik…
American Journal of Physiology-Gastrointestinal and Liver …, 2015journals.physiology.org
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 (ie,
DMT1int/int). DMT1int/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 DMT1int/int mice: 1) blood iron and tissue …
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., DMT1int/int). DMT1int/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 DMT1int/int mice: 1) 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 DMT1int/int mice compared with DMT1+/+ mice but no meaningful change in copper, manganese, or zinc. DMT1int/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 DMT1int/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.
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