Slco1a1-flox 基因敲除小鼠

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产品名称

Slco1a1-flox 基因敲除小鼠

产品编号

S-CKO-10152

品系全称

C57BL/6JCya-Slco1a1em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-28248-Slco1a1-B6J-VA

品系状态

使用本品系发表的文献需注明: Slco1a1-flox 基因敲除小鼠 mice (Strain S-CKO-10152) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型

基本信息

基因研究概述

质控标准

基因
基因全称
solute carrier organic anion transporter family, member 1a1
基因别称
A530084B21,OATP-1,Oatp1,Oatp1a1,Slc21a1
染色体号
Chr 6 (Mouse)
转录本 ID
NCBI: NM_013797.5 | Ensembl: ENSMUST00000042119
修饰方式
条件性基因敲除
靶向范围
Exon 3
敲除长度
~2.0 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:1351891Mice homozygous for a knock-out allele exhibit impaired organic anion transporter activity and urinary metabolomic profiles.
Slco1a1,也称为OATP1A1或有机阴离子转运多肽1A1,是一种重要的膜蛋白,属于溶质载体(SLC)超家族。它主要在肝细胞中表达,负责将多种内源性和外源性化合物从血液转运到肝细胞内,参与药物的代谢和解毒过程。Slco1a1具有广泛的底物特异性,能够转运多种药物、激素和胆汁酸等。因此,Slco1a1在药物的吸收、分布、代谢和排泄等方面发挥着重要作用。此外,Slco1a1还参与胆汁酸的转运和代谢,维持胆汁酸稳态。

Slco1a1的基因表达受到多种因素的调控,包括激素、炎症因子和遗传因素等。例如,研究表明,睾酮可以下调Slco1a1基因的表达,而雌激素可以上调其表达。炎症因子如TNF-α和IFN-γ也可以下调Slco1a1基因的表达。此外,Slco1a1基因存在多种单核苷酸多态性(SNPs),这些SNPs可以影响Slco1a1蛋白的功能和表达水平,从而影响药物的代谢和疗效。

Slco1a1在多种疾病中发挥重要作用,包括糖尿病肾病、非酒精性脂肪性肝病和感染性结肠炎等。例如,在糖尿病肾病模型中,Slco1a1基因的表达下调,这可能与糖尿病肾病的发病机制有关[2]。在非酒精性脂肪性肝病模型中,Slco1a1基因的表达也下调,这可能与胆汁酸代谢紊乱有关[3]。在感染性结肠炎模型中,Slco1a1基因的表达也下调,这可能与药物代谢和解毒功能受损有关[8]。

此外,Slco1a1基因的表达还受到表观遗传调控的影响。例如,研究表明,甲基化可以下调Slco1a1基因的表达,而去甲基化可以上调其表达[5]。此外,Slco1a1基因的启动子区域也存在多种转录因子结合位点,这些转录因子可以调控Slco1a1基因的表达。

综上所述,Slco1a1是一种重要的膜蛋白,在药物的代谢和解毒、胆汁酸的转运和代谢等方面发挥着重要作用。Slco1a1的基因表达受到多种因素的调控,包括激素、炎症因子、遗传因素和表观遗传调控等。Slco1a1在多种疾病中发挥重要作用,包括糖尿病肾病、非酒精性脂肪性肝病和感染性结肠炎等。深入研究Slco1a1的功能和调控机制,有助于更好地理解药物代谢和疾病发生的机制,为疾病的治疗和预防提供新的思路和策略[1,2,3,4,5,6,7,8,9,10]。

参考文献:
1. Monjo, Marta, Rubert, Marina, Ellingsen, Jan Eirik, Lyngstadaas, S Petter. 2010. Rosuvastatin promotes osteoblast differentiation and regulates SLCO1A1 transporter gene expression in MC3T3-E1 cells. In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 26, 647-56. doi:10.1159/000322332. https://pubmed.ncbi.nlm.nih.gov/21063102/
2. Xu, Yushan, Li, Lan, Tang, Ping, Lin, Jie, Zhang, Lihua. 2023. Identifying key genes for diabetic kidney disease by bioinformatics analysis. In BMC nephrology, 24, 305. doi:10.1186/s12882-023-03362-4. https://pubmed.ncbi.nlm.nih.gov/37853335/
3. Tanaka, Naoki, Matsubara, Tsutomu, Krausz, Kristopher W, Patterson, Andrew D, Gonzalez, Frank J. 2012. Disruption of phospholipid and bile acid homeostasis in mice with nonalcoholic steatohepatitis. In Hepatology (Baltimore, Md.), 56, 118-29. doi:10.1002/hep.25630. https://pubmed.ncbi.nlm.nih.gov/22290395/
4. Perea-Jacobo, Ricardo, Muñiz-Salazar, Raquel, Laniado-Laborín, Rafael, Ochoa-Terán, Adrián, Radilla-Chávez, Patricia. 2022. SLCO1B1 and SLC10A1 polymorphism and plasma rifampin concentrations in patients with co-morbidity tuberculosis-diabetes mellitus in Baja California, Mexico. In Tuberculosis (Edinburgh, Scotland), 136, 102248. doi:10.1016/j.tube.2022.102248. https://pubmed.ncbi.nlm.nih.gov/36055153/
5. Dkhil, Mohamed A, Al-Quraishy, Saleh, Abdel-Baki, Abdel-Azeem, Delic, Denis, Wunderlich, Frank. 2014. Epigenetic modifications of gene promoter DNA in the liver of adult female mice masculinized by testosterone. In The Journal of steroid biochemistry and molecular biology, 145, 121-30. doi:10.1016/j.jsbmb.2014.11.006. https://pubmed.ncbi.nlm.nih.gov/25448745/
6. Min, Han, Xu, Y I, Shaowei, You, Shuoshi, Wang, Diancheng, H E. . Gehua Jiejiu Dizhi decoction ameliorates alcoholic fatty liver in mice by regulating lipid and bile acid metabolism and with exertion of antioxidant stress based on 4DLabel-free quantitative proteomic study. In Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan, 44, 277-288. doi:10.19852/j.cnki.jtcm.20231018.001. https://pubmed.ncbi.nlm.nih.gov/38504534/
7. Diao, Meng, Wu, Yimu, Yang, Jialu, Xu, Guotong, Lu, Lixia. 2022. Identification of Novel Key Molecular Signatures in the Pathogenesis of Experimental Diabetic Kidney Disease. In Frontiers in endocrinology, 13, 843721. doi:10.3389/fendo.2022.843721. https://pubmed.ncbi.nlm.nih.gov/35432190/
8. Merrell, Matthew D, Nyagode, Beatrice A, Clarke, John D, Cherrington, Nathan J, Morgan, Edward T. 2013. Selective and cytokine-dependent regulation of hepatic transporters and bile acid homeostasis during infectious colitis in mice. In Drug metabolism and disposition: the biological fate of chemicals, 42, 596-602. doi:10.1124/dmd.113.055525. https://pubmed.ncbi.nlm.nih.gov/24378326/
9. Koishikawa, Tomoki, Kazuki, Kanako, Ohnishi, Rina, Kusuhara, Hiroyuki, Kazuki, Yasuhiro. 2024. Development of an OATP1-humanized transchromosomic mouse model for prediction of hepatic drug uptake in humans. In Drug metabolism and disposition: the biological fate of chemicals, 53, 100028. doi:10.1016/j.dmd.2024.100028. https://pubmed.ncbi.nlm.nih.gov/40023577/
10. Roques, Béatrice B, Leghait, Julien, Lacroix, Marlène Z, Viguié, Catherine, Martin, Pascal G P. 2013. The nuclear receptors pregnane X receptor and constitutive androstane receptor contribute to the impact of fipronil on hepatic gene expression linked to thyroid hormone metabolism. In Biochemical pharmacology, 86, 997-1039. doi:10.1016/j.bcp.2013.08.012. https://pubmed.ncbi.nlm.nih.gov/23962444/