Identification of SLC41A3 as a novel player in magnesium homeostasis

Sci Rep. 2016 Jun 28:6:28565. doi: 10.1038/srep28565.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Homeostasis / physiology*
  • Hypercalciuria / blood
  • Hypercalciuria / genetics
  • Hypercalciuria / urine
  • Magnesium / blood*
  • Magnesium / urine*
  • Mice
  • Mice, Knockout
  • Nephrocalcinosis / blood
  • Nephrocalcinosis / genetics
  • Nephrocalcinosis / urine
  • Renal Tubular Transport, Inborn Errors / blood
  • Renal Tubular Transport, Inborn Errors / genetics
  • Renal Tubular Transport, Inborn Errors / urine


  • Cation Transport Proteins
  • Magnesium

Supplementary concepts

  • Hypomagnesemia primary