title: Disruption of the potassium channel regulatory subunit KCNE2 causes iron-deficient anemia.
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.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Grace
authors.initials: G
authors.lastname: Salsbury
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Cambridge
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Zoe
authors.initials: Z
authors.lastname: McIntyre
authors.affiliation: University of Edinburgh Division of Pathology, Institute of Genetics & Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Arends
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Karp
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Isherwood
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Carl
authors.initials: C
authors.lastname: Shannon
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Hooks
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Ramirez-Solis
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: White
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom. Electronic address: as24@sanger.ac.uk.
authors.forename: Anneliese O
authors.initials: AO
authors.lastname: Speak
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000235:genetics*; D000818:Animals; D066273:Diet, Western; D004909:Erythrocyte Indices; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005293:Ferritins / Q000097:blood; D018740:Genetic Heterogeneity; D006400:Hematocrit; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000172:deficiency; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D024642:Potassium Channels, Voltage-Gated / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012727:Sex Characteristics; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms; D014168:Transferrin / Q000032:analysis
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C498827:Kcne3 protein, mouse; D024642:Potassium Channels, Voltage-Gated; D014168:Transferrin; D004921:Erythropoietin; D005293:Ferritins