| First Author | Ilenwabor BP | Year | 2022 |
| Journal | Am J Physiol Renal Physiol | Volume | 323 |
| Issue | 5 | Pages | F553-F563 |
| PubMed ID | 36049064 | Mgi Jnum | J:344881 |
| Mgi Id | MGI:7579451 | Doi | 10.1152/ajprenal.00101.2022 |
| Citation | Ilenwabor BP, et al. (2022) SLC41A1 knockout mice display normal magnesium homeostasis. Am J Physiol Renal Physiol 323(5):F553-F563 |
| abstractText | 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. |
