title: Identification of SLC41A3 as a novel player in magnesium homeostasis.
abstract: Regulation of the body Mg(2+) balance takes place in the distal convoluted tubule (DCT), where transcellular reabsorption determines the final urinary Mg(2+) excretion. The basolateral Mg(2+) extrusion mechanism in the DCT is still unknown, but recent findings suggest that SLC41 proteins contribute to Mg(2+) extrusion. The aim of this study was, therefore, to characterize the functional role of SLC41A3 in Mg(2+) homeostasis using the Slc41a3 knockout (Slc41a3(-/-)) mouse. By quantitative PCR analysis it was shown that Slc41a3 is the only SLC41 isoform with enriched expression in the DCT. Interestingly, serum and urine electrolyte determinations demonstrated that Slc41a3(-/-) mice suffer from hypomagnesemia. The intestinal Mg(2+) absorption capacity was measured using the stable (25)Mg(2+) isotope in mice fed a low Mg(2+) diet. (25)Mg(2+) uptake was similar in wildtype (Slc41a3(+/+)) and Slc41a3(-/-) mice, although Slc41a3(-/-) animals exhibited increased intestinal mRNA expression of Mg(2+) transporters Trpm6 and Slc41a1. Remarkably, some of the Slc41a3(-/-) mice developed severe unilateral hydronephrosis. In conclusion, SLC41A3 was established as a new factor for Mg(2+) handling.
authors.affiliation: Department of Physiology Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Jeroen H F
authors.initials: JH
authors.lastname: de Baaij
authors.affiliation: Department of Physiology Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Arjona
authors.affiliation: Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: van den Brand
authors.affiliation: Department of Physiology Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Marla
authors.initials: M
authors.lastname: Lavrijsen
authors.affiliation: Department of Physiology Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Anke L L
authors.initials: AL
authors.lastname: Lameris
authors.affiliation: Department of Physiology Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: René J M
authors.initials: RJ
authors.lastname: Bindels
authors.affiliation: Department of Physiology Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Joost G J
authors.initials: JG
authors.lastname: Hoenderop
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D053565:Hypercalciuria / Q000097:blood / Q000235:genetics / Q000652:urine; D008274:Magnesium / Q000097:blood* / Q000652:urine*; D051379:Mice; D018345:Mice, Knockout; D009397:Nephrocalcinosis / Q000097:blood / Q000235:genetics / Q000652:urine; D015499:Renal Tubular Transport, Inborn Errors / Q000097:blood / Q000235:genetics / Q000652:urine
chemical_list: D027682:Cation Transport Proteins; D008274:Magnesium