Slc2a9-KO Mouse

Slc2a9, also known as GLUT9, is a crucial gene encoding a transporter that plays a significant role in regulating serum urate levels. It is one of the key urate transporters in the kidney and gut, with its function directly related to the homeostasis of uric acid [1,5]. Uric acid metabolism is essential for maintaining normal physiological conditions, and Slc2a9 is involved in this important metabolic pathway [6]. Animal models, especially gene-edited models, can be valuable for studying its function.

Multiple studies have explored the relationship between Slc2a9 polymorphisms and gout susceptibility. A meta-analysis showed that the rs12510549, rs16890979, and rs1014290 polymorphisms of SLC2A9 protect against the development of gout in Caucasians and/or Asians [3]. Another meta-analysis indicated that four polymorphisms of SLC2A9 except for rs3733591 are protective SNPs in Caucasians, and rs16890979 and rs1014290 are protective SNPs in both Caucasians and Asians, while rs3733591 may be a susceptibility SNP in Asians [4]. Additionally, a study constructing a gene-edited human embryonic stem cells-derived kidney organoid bearing rs16890979 found that this SNP may compromise the UA absorption functionality of GLUT9 [2].

In conclusion, Slc2a9 is vital for uric acid homeostasis, mainly through its role in urate transport. The findings from studies on its polymorphisms contribute to understanding the genetic basis of gout susceptibility. These insights from model-based research, including the use of gene-edited organoids, help to clarify the function of Slc2a9 in uric acid-related diseases and may provide potential targets for the prevention and treatment of gout [2,3,4].

References:

1. Dalbeth, Nicola, Gosling, Anna L, Gaffo, Angelo, Abhishek, Abhishek. 2021. Gout. In Lancet (London, England), 397, 1843-1855. doi:10.1016/S0140-6736(21)00569-9. https://pubmed.ncbi.nlm.nih.gov/33798500/

2. Wu, Shouhai, Li, Chuang, Li, Yizhen, Zeng, Xiang, Mao, Wei. 2024. SLC2A9 rs16890979 reduces uric acid absorption by kidney organoids. In Frontiers in cell and developmental biology, 11, 1268226. doi:10.3389/fcell.2023.1268226. https://pubmed.ncbi.nlm.nih.gov/38269090/

3. Lee, Y H, Seo, Y H, Kim, J-H, Ji, J D, Song, G G. . Associations between SLC2A9 polymorphisms and gout susceptibility : A meta-analysis. In Zeitschrift fur Rheumatologie, 76, 64-70. doi:10.1007/s00393-016-0070-x. https://pubmed.ncbi.nlm.nih.gov/27052299/

4. Zhang, Xu, Yang, Xiao, Wang, Mengmeng, Zou, Yanfeng, Pan, Faming. 2016. Association between SLC2A9 (GLUT9) gene polymorphisms and gout susceptibility: an updated meta-analysis. In Rheumatology international, 36, 1157-65. doi:10.1007/s00296-016-3503-6. https://pubmed.ncbi.nlm.nih.gov/27255295/

5. So, Alexander, Thorens, Bernard. 2010. Uric acid transport and disease. In The Journal of clinical investigation, 120, 1791-9. doi:10.1172/JCI42344. https://pubmed.ncbi.nlm.nih.gov/20516647/

6. Mandal, Asim K, Mount, David B. 2014. The molecular physiology of uric acid homeostasis. In Annual review of physiology, 77, 323-45. doi:10.1146/annurev-physiol-021113-170343. https://pubmed.ncbi.nlm.nih.gov/25422986/