Abstract |
Iron homeostasis is a dynamic process that is tightly controlled to balance iron uptake, storage, and export. Reduction of dietary iron from the ferric to the ferrous form is required for uptake by solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2 (Slc11a2) into the enterocytes. Both processes are proton dependent and have led to the suggestion of the importance of acidic gastric pH for the absorption of dietary iron. Potassium voltage-gated channel subfamily E, member 2 (KCNE2), in combination with potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1), form a gastric potassium channel essential for gastric acidification. Deficiency of either Kcne2 or Kcnq1 results in achlorhydia, gastric hyperplasia, and neoplasia, but the impact on iron absorption has not, to our knowledge, been investigated. Here we report that Kcne2-deficient mice, in addition to the previously reported phenotypes, also present with iron-deficient anemia. Interestingly, impaired function of KCNQ1 results in iron-deficient anemia in Jervell and Lange-Nielsen syndrome patients. We speculate that impaired function of KCNE2 could result in the same clinical phenotype.
|
Authors | Grace Salsbury, Emma L Cambridge, Zoe McIntyre, Mark J Arends, Natasha A Karp, Christopher Isherwood, Carl Shannon, Yvette Hooks, Sanger Mouse Genetics Project, Ramiro Ramirez-Solis, David J Adams, Jacqueline K White, Anneliese O Speak |
Journal | Experimental hematology
(Exp Hematol)
Vol. 42
Issue 12
Pg. 1053-8.e1
(Dec 2014)
ISSN: 1873-2399 [Electronic] Netherlands |
PMID | 25127743
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2014 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- KCNQ1 Potassium Channel
- KCNQ1 protein, human
- Kcne3 protein, mouse
- Potassium Channels, Voltage-Gated
- Transferrin
- Erythropoietin
- Ferritins
|
Topics |
- Anemia, Iron-Deficiency
(blood, genetics)
- Animals
- Diet, Western
- Erythrocyte Indices
- Erythropoietin
(blood)
- Female
- Ferritins
(blood)
- Genetic Heterogeneity
- Hematocrit
- Humans
- KCNQ1 Potassium Channel
(deficiency)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Phenotype
- Potassium Channels, Voltage-Gated
(deficiency, genetics, physiology)
- Sex Characteristics
- Species Specificity
- Specific Pathogen-Free Organisms
- Transferrin
(analysis)
|