Slc5a2-KO Mouse

Slc5a2, also known as SGLT2, encodes the sodium-glucose cotransporter 2. This protein is crucial for glucose reuptake in the tubular system of the kidney, with SGLT2 responsible for the majority of this reabsorption, while SGLT1 (encoded by SLC5A1) reabsorbs the remainder [1]. Mutations in SLC5A2 are associated with glucosuria, highlighting its significance in maintaining normal glucose homeostasis [1]. Genetically modified mouse models can be valuable in further exploring its function and associated pathways [1].

Mutations in the SLC5A2 gene have been reported to cause familial renal glucosuria (FRG), a condition characterized by isolated glucosuria despite normal blood glucose levels. In Chinese families, several mutations in SLC5A2, including novel ones, have been identified in patients with FRG, such as c.1222G>T/p.(D408Y) and c.1496G>A/p.(R499H), suggesting a key role of SLC5A2 in the pathogenesis of FRG [2,3].

In conclusion, Slc5a2 is essential for renal glucose reabsorption, and its malfunction due to mutations can lead to conditions like familial renal glucosuria. The study of Slc5a2 using gene-modified mouse models can potentially provide more insights into the molecular mechanisms underlying glucose homeostasis and related diseases.

References:

1. Rieg, Timo, Vallon, Volker. 2018. Development of SGLT1 and SGLT2 inhibitors. In Diabetologia, 61, 2079-2086. doi:10.1007/s00125-018-4654-7. https://pubmed.ncbi.nlm.nih.gov/30132033/

2. Li, Shentang, Yang, Yeyi, Huang, Lihua, Kong, Min, Yang, Zuocheng. 2019. A novel compound heterozygous mutation in SLC5A2 contributes to familial renal glucosuria in a Chinese family, and a review of the relevant literature. In Molecular medicine reports, 19, 4364-4376. doi:10.3892/mmr.2019.10110. https://pubmed.ncbi.nlm.nih.gov/30942416/

3. Yu, Lei, Wu, Meng, Hou, Ping, Zhang, Hong. 2020. SLC5A2 mutations, including two novel mutations, responsible for renal glucosuria in Chinese families. In BMC nephrology, 21, 69. doi:10.1186/s12882-020-01725-9. https://pubmed.ncbi.nlm.nih.gov/32111189/