Slc22a1-KO 基因敲除小鼠

下单100%中奖,最高可得千元京东卡
复苏/繁育服务
产品名称

Slc22a1-KO 基因敲除小鼠

产品编号

S-KO-16511

品系全称

C57BL/6JCya-Slc22a1em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-20517-Slc22a1-B6J-VB

品系状态

使用本品系发表的文献需注明: Slc22a1-KO 基因敲除小鼠 mice (Strain S-KO-16511) 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 22 (organic cation transporter), member 1
基因别称
Lx1,Oct1,Orct,Orct1
染色体号
Chr 17 (Mouse)
转录本 ID
NCBI: NM_009202 | Ensembl: ENSMUST00000024596
修饰方式
全身性基因敲除
靶向范围
Exon 2~3
敲除长度
~1.6 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:108111Mice homozygous for a knockout allele are viable, healthy, and fertile but exhibit an impaired liver uptake and direct intestinal excretion of substrate organic cations. Mice homozygous for a different knockout allele show alterations in metformin disposition and its glucose-lowering effects.
基因Slc22a1,也称为有机阳离子转运蛋白1(OCT1),是一种重要的有机阳离子转运蛋白。OCT1在多种细胞类型中表达,包括肝细胞、肾细胞和肠细胞,负责将有机阳离子转运进入细胞内。OCT1在药物代谢中发挥重要作用,参与许多药物的吸收、分布和代谢。例如,OCT1负责将二甲双胍转运进入肝细胞,从而发挥降糖作用。此外,OCT1还参与其他药物的转运,如利多卡因、普鲁卡因和某些抗癌药物。因此,OCT1在药物代谢和个体化医疗中具有重要意义。

OCT1的基因多态性可以影响其转运功能,进而影响药物的药代动力学和药效学。例如,OCT1的rs628031多态性与二甲双胍的药代动力学和HbA1c水平有关。研究表明,携带GG基因型的个体对二甲双胍的疗效更好,而携带AA基因型的个体则对二甲双胍的疗效较差。因此,OCT1的基因多态性可以作为个体化医疗的一个重要指标,帮助医生根据患者的基因型选择合适的药物剂量和治疗方案。

除了二甲双胍,OCT1还参与其他药物的转运,如利多卡因、普鲁卡因和某些抗癌药物。例如,研究表明,OCT1的Met420del多态性与利多卡因的药代动力学有关,携带Met420del基因型的个体对利多卡因的代谢速度更快,需要更高的药物剂量才能达到相同的治疗效果。因此,OCT1的基因多态性还可以用于预测个体对其他药物的代谢和药效学差异。

OCT1的基因多态性还与其他疾病的发生和发展有关。例如,研究表明,OCT1的rs628031多态性与2型糖尿病的易感性有关,携带AA基因型的个体患2型糖尿病的风险更高。此外,OCT1的Met420del多态性与新生儿对O-去甲曲马朵的代谢有关,携带Met420del基因型的个体对O-去甲曲马朵的代谢速度更快,需要更高的药物剂量才能达到相同的镇痛效果。

综上所述,基因Slc22a1编码的OCT1蛋白在药物的吸收、分布和代谢中发挥重要作用。OCT1的基因多态性可以影响其转运功能,进而影响药物的药代动力学和药效学。此外,OCT1的基因多态性还与其他疾病的发生和发展有关。因此,研究OCT1的基因多态性对于个体化医疗和疾病预防具有重要意义[1][2][3][4][5][6][7][8][9][10]。

参考文献:
1. Pradana, A D, Kristin, E, Nugrahaningsih, D A A, Nugroho, A K, Pinzon, R T. . Influence of Solute Carrier Family 22 Member 1 (SLC22A1) Gene Polymorphism on Metformin Pharmacokinetics and HbA1c Levels: A Systematic Review. In Current diabetes reviews, 20, e070823219470. doi:10.2174/1573399820666230807145202. https://pubmed.ncbi.nlm.nih.gov/37550919/
2. Long, Guanghui, Zhang, Guangtao, Zhang, Fangting, Yang, Dengke, Yang, Yinke. . Relationship Between SLC22A1 and SLC22A4 Gene Polymorphisms and Risk of Type 2 Diabetes in Chinese Han Population. In Clinical laboratory, 64, 1357-1361. doi:10.7754/Clin.Lab.2018.180129. https://pubmed.ncbi.nlm.nih.gov/30274012/
3. Singh, Shalini, Shukla, Ashwin Kumar, Usman, Kauser, Banerjee, Monisha. 2023. Pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) in newly diagnosed Indian type 2 diabetes patients undergoing metformin monotherapy. In Pharmacogenetics and genomics, 33, 51-58. doi:10.1097/FPC.0000000000000493. https://pubmed.ncbi.nlm.nih.gov/36853844/
4. Ningrum, Vitarani Dwi Ananda, Sadewa, Ahmad Hamim, Ikawati, Zullies, Ikhsan, M Robikhul, Fajriyah, Rohmatul. 2022. The influence of metformin transporter gene SLC22A1 and SLC47A1 variants on steady-state pharmacokinetics and glycemic response. In PloS one, 17, e0271410. doi:10.1371/journal.pone.0271410. https://pubmed.ncbi.nlm.nih.gov/35905099/
5. Le, Jiamei, Chen, Yilong, Yang, Wei, Chen, Ligong, Ye, Jianping. 2023. Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus. In Acta pharmaceutica Sinica. B, 14, 437-454. doi:10.1016/j.apsb.2023.09.004. https://pubmed.ncbi.nlm.nih.gov/38322335/
6. Ningrum, Vitarani DA, Istikharah, Rochmy, Firmansyah, Rheza. 2019. Allele Frequency of SLC22A1 Met420del Metformin Main Transporter Encoding Gene among Javanese-Indonesian Population. In Open access Macedonian journal of medical sciences, 7, 378-383. doi:10.3889/oamjms.2019.087. https://pubmed.ncbi.nlm.nih.gov/30834005/
7. Matic, Maja, de Wildt, Saskia N, Elens, Laure, van Schaik, Ron H N, Allegaert, Karel. . SLC22A1/OCT1 Genotype Affects O-desmethyltramadol Exposure in Newborn Infants. In Therapeutic drug monitoring, 38, 487-92. doi:10.1097/FTD.0000000000000307. https://pubmed.ncbi.nlm.nih.gov/27082504/
8. Reséndiz-Abarca, Carlos Alberto, Flores-Alfaro, Eugenia, Suárez-Sánchez, Fernando, Wacher-Rodarte, Niels Agustín, Gómez-Zamudio, Jaime Héctor. 2019. Altered Glycemic Control Associated With Polymorphisms in the SLC22A1 (OCT1) Gene in a Mexican Population With Type 2 Diabetes Mellitus Treated With Metformin: A Cohort Study. In Journal of clinical pharmacology, 59, 1384-1390. doi:10.1002/jcph.1425. https://pubmed.ncbi.nlm.nih.gov/31012983/
9. Cahua-Pablo, José Ángel, Gómez-Zamudio, Jaime Héctor, Reséndiz-Abarca, Carlos Alberto, Zubillaga-Guerrero, Ma Isabel, Flores-Alfaro, Eugenia. 2021. Genetic variants in SLC22A1 are related to serum lipid levels in Mexican women. In Lipids, 57, 105-114. doi:10.1002/lipd.12334. https://pubmed.ncbi.nlm.nih.gov/34927264/
10. Degaga, Abraham, Sirgu, Sisay, Huri, Hasniza Zaman, Engidawork, Ephrem, Shibeshi, Workineh. 2023. Association of Met420del Variant of Metformin Transporter Gene SLC22A1 with Metformin Treatment Response in Ethiopian Patients with Type 2 Diabetes. In Diabetes, metabolic syndrome and obesity : targets and therapy, 16, 2523-2535. doi:10.2147/DMSO.S426632. https://pubmed.ncbi.nlm.nih.gov/37641646/