Slc5a2-KO 基因敲除小鼠

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产品名称

Slc5a2-KO 基因敲除小鼠

产品编号

S-KO-07665

品系全称

C57BL/6JCya-Slc5a2em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-246787-Slc5a2-B6J-VA

品系状态

使用本品系发表的文献需注明: Slc5a2-KO 基因敲除小鼠 mice (Strain S-KO-07665) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量

基本信息

基因研究概述

质控标准

基因
基因全称
solute carrier family 5 (sodium/glucose cotransporter), member 2
基因别称
Sglt2
染色体号
Chr 7 (Mouse)
转录本 ID
NCBI: NM_133254.5 | Ensembl: ENSMUST00000118169
修饰方式
全身性基因敲除
靶向范围
Exon 4~5
敲除长度
~1.4 kb
品系说明
该品系是基于策略设计时的数据库信息制作而成,建议您在购买前查询最新的数据库和相关文献,以获取最准确的表型信息。
表型提示
MGI:2181411Mice homozygous for a null allele exhibit increased urine glucose, increased eating and drinking behaviors, increased circulating renin activity, decreased urine osmolality, decreased serum aldosterone levels, polyuria, and decreased glucose renal reabsorption.
SLC5A2,也称为钠-葡萄糖协同转运蛋白2(SGLT2),是一种在肾脏近端肾小管上皮细胞中表达的蛋白。SGLT2负责将葡萄糖从肾小球滤液中重吸收回血液中,维持血糖水平的稳定。SGLT2的功能障碍可能导致葡萄糖在尿液中丢失,称为家族性肾性糖尿症(FRG)。此外,SGLT2的抑制剂被广泛用于治疗2型糖尿病,通过促进尿液中葡萄糖的排泄来降低血糖水平。

研究表明,SLC5A2基因的突变与FRG的发生密切相关。某些SLC5A2基因的突变可能导致蛋白质结构改变,进而影响其功能,导致葡萄糖不能被有效重吸收。例如,一些突变可能干扰蛋白质的折叠,使其无法正确地嵌入细胞膜中,从而影响葡萄糖的重吸收过程。

除了FRG,SLC5A2基因的变异还可能影响2型糖尿病的治疗效果。研究表明,SLC5A2基因的某些多态性可能与患者对SGLT2抑制剂的反应性相关。例如,SLC5A2基因的某些变异可能影响药物的代谢和作用机制,导致患者对药物的敏感性发生变化。

此外,SLC5A2基因的功能也与心血管疾病的发生和发展有关。SGLT2抑制剂已被证明可以降低2型糖尿病患者的心血管疾病风险,但其具体机制尚不完全清楚。研究表明,SGLT2抑制剂可能通过影响胆碱代谢物和炎症标志物等代谢途径来降低心血管疾病风险。

综上所述,SLC5A2基因在葡萄糖重吸收、2型糖尿病治疗和心血管疾病的发生发展中发挥着重要作用。进一步研究SLC5A2基因的功能和变异对疾病的预测和治疗具有重要意义。

参考文献:
1. Xu, Min, Zheng, Jie, Hou, Tianzhichao, Bi, Yufang, Wang, Weiqing. SGLT2 Inhibition, Choline Metabolites, and Cardiometabolic Diseases: A Mediation Mendelian Randomization Study. Diabetes care, 45, 2718-2728. doi:10.2337/dc22-0323.
2. Li, Jiang, Yu, Yuefeng, Sun, Ying, Lu, Yingli, Wang, Ningjian. SGLT2 inhibition, circulating metabolites, and atrial fibrillation: a Mendelian randomization study. Cardiovascular diabetology, 22, 278. doi:10.1186/s12933-023-02019-8.
3. Fang, Xinyi, Miao, Runyu, Wei, Jiahua, Wu, Haoran, Tian, Jiaxing. Advances in multi-omics study of biomarkers of glycolipid metabolism disorder. Computational and structural biotechnology journal, 20, 5935-5951. doi:10.1016/j.csbj.2022.10.030.
4. Rieg, Timo, Vallon, Volker. Development of SGLT1 and SGLT2 inhibitors. Diabetologia, 61, 2079-2086. doi:10.1007/s00125-018-4654-7.
5. Guo, Wenqin, Zhao, Lingyue, Huang, Weichao, Peng, Changnong, Yan, Hongbing. Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study. Cardiovascular diabetology, 23, 118. doi:10.1186/s12933-024-02210-5.
6. Xu, Bo, Li, Shaoqian, Kang, Bo, Tang, Fan, Zhou, Jiecan. Role of SLC5A2 polymorphisms and effects of genetic polymorphism on sodium glucose cotransporter 2 inhibitorsinhibitor response. Molecular biology reports, 50, 9637-9647. doi:10.1007/s11033-023-08836-0.
7. Wang, Sai, Wang, Yixiu, Wang, Jinchao, Bottillo, Irene, Shao, Leping. Six Exonic Variants in the SLC5A2 Gene Cause Exon Skipping in a Minigene Assay. Frontiers in genetics, 11, 585064. doi:10.3389/fgene.2020.585064.
8. Dorum, Sevil, Erdoğan, Hakan, Köksoy, Adem Yasin, Topak, Ali, Görükmez, Özlem. Clinical features of pediatric renal glucosuria cases due to SLC5A2 gene variants. Pediatrics international : official journal of the Japan Pediatric Society, 64, e14948. doi:10.1111/ped.14948.
9. Panico, Cristina, Felicetta, Arianna, Kunderfranco, Paolo, Greco, Carolina M, Condorelli, Gianluigi. Single-Cell RNA Sequencing Reveals Metabolic Stress-Dependent Activation of Cardiac Macrophages in a Model of Dyslipidemia-Induced Diastolic Dysfunction. Circulation, 150, 1517-1532. doi:10.1161/CIRCULATIONAHA.122.062984.
10. Tomita, Issei, Kume, Shinji, Sugahara, Sho, Araki, Shin-Ichi, Maegawa, Hiroshi. SGLT2 Inhibition Mediates Protection from Diabetic Kidney Disease by Promoting Ketone Body-Induced mTORC1 Inhibition. Cell metabolism, 32, 404-419.e6. doi:10.1016/j.cmet.2020.06.020.
参考文献: