title: Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival.
abstract: Mg2+regulates many physiological processes and signalling pathways. However, little is known about the mechanisms underlying the organismal balance of Mg2+. Capitalizing on a set of newly generated mouse models, we provide an integrated mechanistic model of the regulation of organismal Mg2+balance during prenatal development and in adult mice by the ion channel TRPM6. We show that TRPM6 activity in the placenta and yolk sac is essential for embryonic development. In adult mice, TRPM6 is required in the intestine to maintain organismal Mg2+balance, but is dispensable in the kidney.Trpm6inactivation in adult mice leads to a shortened lifespan, growth deficit and metabolic alterations indicative of impaired energy balance. Dietary Mg2+supplementation not only rescues all phenotypes displayed byTrpm6-deficient adult mice, but also may extend the lifespan of wildtype mice. Hence, maintenance of organismal Mg2+balance by TRPM6 is crucial for prenatal development and survival to adulthood.
authors.affiliation: Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Vladimir
authors.identifier: 0000-0002-6042-4193
authors.initials: V
authors.lastname: Chubanov
authors.affiliation: Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferioli
authors.affiliation: Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Wisnowsky
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
authors.forename: David G
authors.identifier: 0000-0002-4115-9371
authors.initials: DG
authors.lastname: Simmons
authors.affiliation: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Leitzinger
authors.affiliation: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Einer
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany.|German Center for Diabetes Research, Munich, Germany.
authors.forename: Wenke
authors.initials: W
authors.lastname: Jonas
authors.affiliation: Princeton Institute of Life Sciences, Princeton, United States.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Shymkiv
authors.affiliation: Institute of Pathology, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Bartsch
authors.affiliation: Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.|Department of Vascular Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Attila
authors.initials: A
authors.lastname: Braun
authors.affiliation: Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Banu
authors.initials: B
authors.lastname: Akdogan
authors.affiliation: Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Mittermeier
authors.affiliation: Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Sytik
authors.affiliation: Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum Munich, Neuherberg, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Torben
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Vindi
authors.initials: V
authors.lastname: Jurinovic
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Emiel Pc
authors.initials: EP
authors.lastname: van der Vorst
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig Maximilian University of Munich, Munich, Germany.|German Centre for Cardiovascular Research, Munich Heart Alliance, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum Munich, Neuherberg, Germany.|German Center for Lung Research, Munich, Germany.
authors.forename: Önder A
authors.initials: ÖA
authors.lastname: Yildirim
authors.affiliation: Institute of Pathology, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Sotlar
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany.|German Center for Diabetes Research, Munich, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Schürmann
authors.affiliation: Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Susanna
authors.identifier: 0000-0002-4684-0385
authors.initials: S
authors.lastname: Zierler
authors.affiliation: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Zischka
authors.affiliation: Princeton Institute of Life Sciences, Princeton, United States.|Department of Cellular and Molecular Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, United States.
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Ryazanov
authors.affiliation: Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany.|German Centre for Cardiovascular Research, Munich Heart Alliance, Munich, Germany.|Comprehensive Pneumology Center Munich, German Center for Lung Research, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gudermann
mesh_terms: D000818:Animals; D047108:Embryonic Development; D005260:Female; D055786:Gene Knockout Techniques; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D051379:Mice; D010920:Placenta / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D016019:Survival Analysis; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D015017:Yolk Sac / Q000201:enzymology / Q000378:metabolism
chemical_list: D050053:TRPM Cation Channels; C530168:Trpm6 protein, mouse; D008274:Magnesium
keywords: biophysics; human biology; intestine; kidney; longevity; magnesium; medicine; mouse; placenta; structural biology; trophoblast stem cells