SLC41A1 knockout mice display normal magnesium homeostasis

• Published in: American journal of physiology. Renal physiology 2022-11, Vol.323 (5), p.F553-F563
• Main Authors: Ilenwabor, Barnabas P, Franken, Gijs A C, Sponder, Gerhard, Bos, Caro, Racay, Peter, Kolisek, Martin, Hoenderop, Joost G J, de Baaij, Jeroen H F
• Format: Article
• Language: English
• Subjects: Animals; Cation Transport Proteins - genetics; Cations; Cyclins - metabolism; Dietary restrictions; Genotypes; Homeostasis; Kidney Tubules, Distal - metabolism; Kidneys; Magnesium; Magnesium - metabolism; Metal ions; Mice; Mice, Knockout; Mice, Transgenic; Reabsorption; Rodents; Transient receptor potential proteins; TRPM Cation Channels - genetics; TRPM Cation Channels - metabolism
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00101.2022

Transcellular Mg reabsorption in the distal convoluted tubule (DCT) of the kidneys plays an important role in maintaining systemic Mg homeostasis. SLC41A1 is a Na /Mg exchanger that mediates Mg efflux from cells and is hypothesized to facilitate basolateral extrusion of Mg in the DCT. In this study, we generated a SLC41A1 knockout mouse model to examine the role of SLC41A1 in Mg homeostasis. mice exhibited similar serum and urine Mg levels as their wild-type littermates. Dietary restriction of Mg resulted in reduced serum Mg concentration and urinary Mg excretion, which was similar in the wild-type and knockout groups. Expression of genes encoding Mg channels and transporters such as transient receptor potential melastatin 6 ( ), transient receptor potential melastatin 7 ( ), cyclin and CBS domain divalent metal cation transport mediator 2 ( ), and were unchanged based on genotype. We investigated the potential redundancy of SLC41A1 and its homolog SLC41A3 by generating a double knockout mouse. Although knockout mice showed significantly reduced serum Mg compared with wild-type and knockout groups, double knockout mice displayed similar serum Mg levels as knockout mice. In conclusion, our data show that SLC41A1 is not involved in the regulation of systemic Mg homeostasis in mice. Our data also demonstrate that SLC41A1 does not compensate for the loss of SLC41A3, suggesting different functions of these SLC41 proteins in vivo. SLC41A1 has been hypothesized to mediate Mg extrusion in the distal convoluted tubule and thus regulate Mg homeostasis. This study investigated the role of SLC41A1 in Mg homeostasis in vivo using a transgenic mouse model. Our results demonstrate that SLC41A1 is not required to maintain normal Mg balance in mice. We also show that SLC41A3 is more important than SLC41A1 in regulating systemic Mg levels.