Identification of GLUT12/SLC2A12 as a urate transporter that regulates the blood urate level in hyperuricemia model mice

Proceedings of the National Academy of Sciences of the United States of America
Yu ToyodaHiroshi Suzuki

Abstract

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.

References

Jan 18, 1994·Proceedings of the National Academy of Sciences of the United States of America·X WuC T Caskey
Nov 26, 2008·American Journal of Human Genetics·Hirotaka MatsuoNariyoshi Shinomiya
Dec 30, 2015·Genesis : the Journal of Genetics and Development·Harumi NakaoAtsu Aiba
May 14, 2016·Biological & Pharmaceutical Bulletin·Tamaki WatanabeMakoto Hosoyamada
Sep 29, 2019·Nature Reviews. Disease Primers·Nicola DalbethLisa K Stamp

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