title: SLC39A14 Is Required for the Development of Hepatocellular Iron Overload in Murine Models of Hereditary Hemochromatosis.
abstract: Nearly all forms of hereditary hemochromatosis are characterized by pathological iron accumulation in the liver, pancreas, and heart. These tissues preferentially load iron because they take up non-transferrin-bound iron (NTBI), which appears in the plasma during iron overload. Yet, how tissues take up NTBI is largely unknown. We report that ablation of Slc39a14, the gene coding for solute carrier SLC39A14 (also called ZIP14), in mice markedly reduced the uptake of plasma NTBI by the liver and pancreas. To test the role of SLC39A14 in tissue iron loading, we crossed Slc39a14(-/-) mice with Hfe(-/-) and Hfe2(-/-) mice, animal models of type 1 and type 2 (juvenile) hemochromatosis, respectively. Slc39a14 deficiency in hemochromatotic mice greatly diminished iron loading of the liver and prevented iron deposition in hepatocytes and pancreatic acinar cells. The data suggest that inhibition of SLC39A14 may mitigate hepatic and pancreatic iron loading and associated pathologies in iron overload disorders.
authors.affiliation: Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Supak
authors.initials: S
authors.lastname: Jenkitkasemwong
authors.affiliation: Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Coffey
authors.affiliation: Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Chan
authors.affiliation: Department of Surgery, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Biel
authors.affiliation: Department of Surgery, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Deutsches Rheuma-Forschungszentrum Berlin, Osteoimmunology, Charitéplatz, 10117 Berlin, Germany.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hojyo
authors.affiliation: RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Shinagawa 142-8666, Japan; Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8055, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukada
authors.affiliation: Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA. Electronic address: mknutson@ufl.edu.
authors.forename: Mitchell D
authors.initials: MD
authors.lastname: Knutson
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D017353:Gene Deletion; D006432:Hemochromatosis / Q000150:complications / Q000151:congenital* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D019190:Iron Overload / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000378:metabolism / Q000473:pathology
chemical_list: D027682:Cation Transport Proteins; C500556:SLC39A14 protein, mouse