Recent genome-wide association studies have revealed some genetic loci associated with serum uric acid levels and susceptibility to gout/hyperuricemia which contain potential candidates of physiologically important urate transporters. One of these novel loci is located upstream of SGK1 and SLC2A12, suggesting that variations in these genes increase the risks of hyperuricemia and gout. We herein focused on SLC2A12 encoding a transporter, GLUT12, the physiological function of which remains unclear. As GLUT12 belongs to the same protein family as a well-recognized urate transporter GLUT9, we hypothesized that GLUT12 mediates membrane transport of urate. Therefore, we conducted functional assays and analyzed Glut12 knockout hyperuricemia model mice, generated using the CRISPR-Cas9 system. Our results revealed that GLUT12 acts as a physiological urate transporter and its dysfunction elevates the blood urate concentration. This study provides insights into the deeper understanding of the urate regulatory system in the body, which is also important for pathophysiology of gout/hyperuricemia.

最近的全基因组关联研究已经揭示了一些与血清尿酸水平和痛风/高尿酸血症易感性相关的基因位点，其中可能含有重要的生理性尿酸盐转运蛋白。这些新基因座之一位于SGK1和SLC2A12的上游，表明这些基因的变异会增加高尿酸血症和痛风的风险。本文我们针对SLC2A12编码转运，GLUT12，生理功能，其中仍不清楚。由于GLUT12与公认的尿酸盐转运蛋白GLUT9属于同一蛋白质家族，我们假设GLUT12介导尿酸盐的膜转运。因此，我们进行了功能测定并分析了Glut12使用CRISPR-Cas9系统生成的基因敲除高尿酸血症模型小鼠。我们的结果表明，GLUT12充当生理尿酸盐转运蛋白，其功能障碍会升高血液尿酸盐浓度。这项研究为深入了解体内的尿酸调节系统提供了见识，这对于痛风/高尿酸血症的病理生理学也很重要。