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Media type:
E-Article
Title:
Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese
Contributor:
Shawki, Ali;
Anthony, Sarah R.;
Nose, Yasuhiro;
Engevik, Melinda A.;
Niespodzany, Eric J.;
Barrientos, Tomasa;
Öhrvik, Helena;
Worrell, Roger T.;
Thiele, Dennis J.;
Mackenzie, Bryan
imprint:
American Physiological Society, 2015
Published in:American Journal of Physiology-Gastrointestinal and Liver Physiology
Language:
English
DOI:
10.1152/ajpgi.00160.2015
ISSN:
0193-1857;
1522-1547
Origination:
Footnote:
Description:
<jats:p>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<jats:sup>int/int</jats:sup>). DMT1<jats:sup>int/int</jats:sup>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<jats:sup>int/int</jats:sup>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<jats:sup>int/int</jats:sup>mice compared with DMT1<jats:sup>+/+</jats:sup>mice but no meaningful change in copper, manganese, or zinc. DMT1<jats:sup>int/int</jats:sup>mice absorbed<jats:sup>64</jats:sup>Cu and<jats:sup>54</jats:sup>Mn from an intragastric dose to the same extent as did DMT1<jats:sup>+/+</jats:sup>mice but the absorption of<jats:sup>59</jats:sup>Fe was virtually abolished in DMT1<jats:sup>int/int</jats:sup>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.</jats:p>