Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Institute of Veterinary Physiology, Freie Universität Berlin, Berlin, Germany.
Am J Physiol Renal Physiol. 2022 Nov 1;323(5):F553-F563. doi: 10.1152/ajprenal.00101.2022. Epub 2022 Sep 1.
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.
肾脏远曲小管（DCT）中的细胞间镁重吸收在维持全身镁稳态中发挥重要作用。SLC41A1 是一种 Na/Mg 交换器，介导细胞内镁外流，据推测可促进 DCT 中镁的基底外侧外排。在这项研究中，我们构建了 SLC41A1 敲除小鼠模型，以研究 SLC41A1 在镁稳态中的作用。SLC41A1 敲除小鼠的血清和尿镁水平与野生型同窝仔鼠相似。镁饮食限制导致血清镁浓度降低和尿镁排泄减少，野生型和敲除组之间的变化相似。根据基因型，编码镁通道和转运体的基因（如瞬时受体电位 melastatin 6 ()、瞬时受体电位 melastatin 7 ()、细胞周期蛋白和 CBS 结构域二价金属阳离子转运调节剂 2 () 和 ）的表达没有变化。我们通过生成双敲除小鼠来研究 SLC41A1 及其同源物 SLC41A3 的潜在冗余性。尽管 SLC41A1 敲除小鼠的血清镁明显低于野生型和 SLC41A3 敲除小鼠，但双敲除小鼠的血清镁水平与 SLC41A3 敲除小鼠相似。总之，我们的数据表明 SLC41A1 不参与调节小鼠的全身镁稳态。我们的数据还表明 SLC41A1 不能代偿 SLC41A3 的缺失，这表明这些 SLC41 蛋白在体内具有不同的功能。SLC41A1 被假设介导 DCT 中的镁外排，从而调节镁稳态。本研究使用转基因小鼠模型研究了 SLC41A1 在体内镁稳态中的作用。我们的结果表明，SLC41A1 对于维持小鼠的正常镁平衡不是必需的。我们还表明，SLC41A3 在调节全身镁水平方面比 SLC41A1 更重要。
