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: 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 DMT1(int/int) mice compared with DMT1(+/+) mice but no meaningful 
change in copper, manganese, or zinc. DMT1(int/int) mice absorbed (64)Cu and 
(54)Mn from an intragastric dose to the same extent as did DMT1(+/+) mice but 
the absorption of (59)Fe 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.