SLC41A1 knockout mice display normal magnesium homeostasis.

Transcellular Mg 2+ reabsorption in the distal convoluted tubule (DCT) of the kidneys plays an important role in maintaining systemic Mg 2+ homeostasis. SLC41A1 is a Na + /Mg 2+ exchanger that mediates Mg 2+ efflux from cells and is hypothesized to facilitate basolateral extrusion of Mg 2+ in the DCT. In this study, we generated a SLC41A1 knockout mouse model to examine the role of SLC41A1 in Mg 2+ homeostasis. Slc41a1 -/- mice exhibited similar serum and urine Mg 2+ levels as their wild-type littermates. Dietary restriction of Mg 2+ resulted in reduced serum Mg 2+ concentration and urinary Mg 2+ excretion, which was similar in the wild-type and knockout groups. Expression of genes encoding Mg 2+ channels and transporters such as transient receptor potential melastatin 6 ( Trpm6 ), transient receptor potential melastatin 7 ( Trpm7 ), cyclin and CBS domain divalent metal cation transport mediator 2 ( Cnnm2 ), and Slc41a3 were unchanged based on genotype. We investigated the potential redundancy of SLC41A1 and its homolog SLC41A3 by generating a double knockout mouse. Although Slc41a3 -/- knockout mice showed significantly reduced serum Mg 2+ compared with wild-type and Slc41a1 -/- knockout groups, double knockout mice displayed similar serum Mg 2+ levels as Slc41a3 -/- knockout mice. In conclusion, our data show that SLC41A1 is not involved in the regulation of systemic Mg 2+ 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. NEW & NOTEWORTHY SLC41A1 has been hypothesized to mediate Mg 2+ extrusion in the distal convoluted tubule and thus regulate Mg 2+ homeostasis. This study investigated the role of SLC41A1 in Mg 2+ homeostasis in vivo using a transgenic mouse model. Our results demonstrate that SLC41A1 is not required to maintain normal Mg 2+ balance in mice. We also show that SLC41A3 is more important than SLC41A1 in regulating systemic Mg 2+ levels.