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

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2015-10, Vol.309 (8), p.G635-G647
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Anemia; Anemia, Hypochromic - genetics; Anemia, Hypochromic - pathology; Animals; Cation Transport Proteins - genetics; Cation Transport Proteins - metabolism; Copper; Copper - metabolism; copper absorption; Gene Expression Regulation - physiology; Homeostasis - physiology; Intestinal Absorption - physiology; Iron; Iron - metabolism; iron deficiency; iron-deficiency anemia; iron-refractive iron-deficiency anemia; Manganese - metabolism; manganese absorption; Manganese compounds; Mice; Mice, Knockout; Nutrient Sensing, Nutrition, and Metabolism; Rodents; SLC11A2; Tissues; Zinc - metabolism
• ISSN: 0193-1857; 1522-1547; 1522-1547
• DOI: 10.1152/ajpgi.00160.2015

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.