Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese
2015 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 309, no 8, G635-G647 p.Article in journal (Refereed) PublishedText
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 Cu-64 and Mn-54 from an intragastric dose to the same extent as did DMT1(+/+) mice but the absorption of Fe-59 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.
Place, publisher, year, edition, pages
2015. Vol. 309, no 8, G635-G647 p.
copper absorption, iron deficiency, iron-deficiency anemia, iron-refractive iron-deficiency anemia, manganese absorption, SLC11A2, zinc metabolism
Gastroenterology and Hepatology Physiology
IdentifiersURN: urn:nbn:se:uu:diva-268700DOI: 10.1152/ajpgi.00160.2015ISI: 000364068300003PubMedID: 26294671OAI: oai:DiVA.org:uu-268700DiVA: diva2:880542