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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Shawki, A; Anthony, SR; Nose, Y; Engevik, MA; Niespodzany, EJ; Barrientos, T; Öhrvik, H; Worrell, RT; Thiele, DJ; Mackenzie, B

Published Date

  • October 15, 2015

Published In

Volume / Issue

  • 309 / 8

Start / End Page

  • G635 - G647

PubMed ID

  • 26294671

Pubmed Central ID

  • 26294671

Electronic International Standard Serial Number (EISSN)

  • 1522-1547

Digital Object Identifier (DOI)

  • 10.1152/ajpgi.00160.2015

Language

  • eng

Conference Location

  • United States