Tm6sf2-KO 基因敲除小鼠

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产品名称

Tm6sf2-KO 基因敲除小鼠

产品编号

S-KO-00541

品系全称

C57BL/6NCya-Tm6sf2em1/Cya

品系背景

C57BL/6NCya

品系编号

KOCMP-107770-Tm6sf2-B6N-VA

品系状态

使用本品系发表的文献需注明: Tm6sf2-KO 基因敲除小鼠 mice (Strain S-KO-00541) 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
transmembrane 6 superfamily member 2
基因别称
-
染色体号
Chr 8 (Mouse)
转录本 ID
NCBI: NM_001293795 | Ensembl: ENSMUST00000110160
修饰方式
全身性基因敲除
靶向范围
Exon 2~9
敲除长度
~4.6 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:1933210Homozygotes for a null allele show hepatosteatosis, hypocholesterolemia, increased serum alanine transaminase level, reduced VLDL-TG secretion, small VLDL particles, and lipid accumulation in enterocytes. Homozygotes for another null allele show reduced total cholesterol and LDL cholesterol levels.
TM6SF2,也称为Transmembrane 6 superfamily member 2,是一种位于19p12位点的基因,其编码的蛋白质在调节血浆脂质水平方面发挥着重要作用[2]。TM6SF2基因的变异与多种疾病的发生和发展相关,包括心血管疾病(CVD)、非酒精性脂肪肝病(NAFLD)和肝细胞癌(HCC)等[1,4,5,6,7,8,9,10]。

在心血管疾病方面,TM6SF2基因的变异与动脉粥样硬化的发生和发展相关。一项研究通过构建骨髓细胞特异性Tm6sf2基因敲除小鼠,发现敲除Tm6sf2基因可以抑制动脉粥样硬化的发生,并减少泡沫细胞的形成,同时不影响血浆脂质水平[5]。这表明TM6SF2基因可能在动脉粥样硬化的发生和发展中起着重要的调节作用。

在非酒精性脂肪肝病方面,TM6SF2基因的变异与NAFLD的发生和发展密切相关。多项研究发现,TM6SF2基因的变异与NAFLD患者的肝脂肪变性和纤维化程度相关,并可能成为治疗NAFLD的潜在靶点[1,6,9]。此外,TM6SF2基因的变异还与非酒精性脂肪性肝炎(NASH)的发生和发展相关[6]。

在肝细胞癌方面,TM6SF2基因的变异与HCC的发生风险相关。一项荟萃分析发现,TM6SF2基因的变异与HCC的发生风险显著相关,表明TM6SF2基因可能成为HCC的潜在诊断和治疗的靶点[4]。

除了在疾病方面的作用,TM6SF2基因还在脂质代谢中发挥着重要作用。研究表明,TM6SF2基因参与调节肠道胆固醇吸收和肝脏胆固醇生物合成和转运,从而影响血浆脂质水平[2]。此外,TM6SF2基因的变异还与非酒精性高脂血症的发生相关,表明TM6SF2基因可能在脂质代谢中起着重要的调节作用[3]。

综上所述,TM6SF2基因在调节血浆脂质水平、心血管疾病、非酒精性脂肪肝病和肝细胞癌等方面发挥着重要作用。TM6SF2基因的变异与多种疾病的发生和发展相关,并可能成为治疗这些疾病的潜在靶点。深入研究TM6SF2基因的功能和作用机制,有助于更好地理解脂质代谢和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Basyte-Bacevice, Viktorija, Skieceviciene, Jurgita, Valantiene, Irena, Lammert, Frank, Kupcinskas, Juozas. 2019. TM6SF2 and MBOAT7 Gene Variants in Liver Fibrosis and Cirrhosis. In International journal of molecular sciences, 20, . doi:10.3390/ijms20061277. https://pubmed.ncbi.nlm.nih.gov/30875804/
2. Li, Ting-Ting, Li, Tao-Hua, Peng, Juan, Zheng, Xi-Long, Tang, Zhi-Han. 2017. TM6SF2: A novel target for plasma lipid regulation. In Atherosclerosis, 268, 170-176. doi:10.1016/j.atherosclerosis.2017.11.033. https://pubmed.ncbi.nlm.nih.gov/29232562/
3. Deng, Guo-Xiong, Yin, Rui-Xing, Guan, Yao-Zong, Wu, Jin-Zhen, Miao, Liu. 2020. Association of the NCAN-TM6SF2-CILP2-PBX4-SUGP1-MAU2 SNPs and gene-gene and gene-environment interactions with serum lipid levels. In Aging, 12, 11893-11913. doi:10.18632/aging.103361. https://pubmed.ncbi.nlm.nih.gov/32568739/
4. Tang, Shan, Zhang, Jing, Mei, Ting-Ting, Qiu, Li-Xia, Yu, Hai-Bin. 2019. Association of TM6SF2 rs58542926 T/C gene polymorphism with hepatocellular carcinoma: a meta-analysis. In BMC cancer, 19, 1128. doi:10.1186/s12885-019-6173-4. https://pubmed.ncbi.nlm.nih.gov/31752753/
5. Zhu, Wenzhen, Liang, Wenying, Lu, Haocheng, Chen, Y Eugene, Guo, Yanhong. 2022. Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis. In Cells, 11, . doi:10.3390/cells11182877. https://pubmed.ncbi.nlm.nih.gov/36139452/
6. Trépo, Eric, Valenti, Luca. 2020. Update on NAFLD genetics: From new variants to the clinic. In Journal of hepatology, 72, 1196-1209. doi:10.1016/j.jhep.2020.02.020. https://pubmed.ncbi.nlm.nih.gov/32145256/
7. Chouik, Yasmina, Di Filippo, Mathilde, Radenne, Sylvie, Moulin, Philippe, Levrero, Massimo. 2024. Combination of heterozygous APOB gene mutation with PNPLA3 and TM6SF2 variants promotes steatotic liver disease, cirrhosis and HCC development. In Liver international : official journal of the International Association for the Study of the Liver, 44, 1474-1477. doi:10.1111/liv.15837. https://pubmed.ncbi.nlm.nih.gov/38421084/
8. Luo, Fei, Smagris, Eriks, Martin, Sarah A, Hobbs, Helen H, Cohen, Jonathan C. 2021. Hepatic TM6SF2 Is Required for Lipidation of VLDL in a Pre-Golgi Compartment in Mice and Rats. In Cellular and molecular gastroenterology and hepatology, 13, 879-899. doi:10.1016/j.jcmgh.2021.12.008. https://pubmed.ncbi.nlm.nih.gov/34923175/
9. Anstee, Quentin M, Darlay, Rebecca, Cockell, Simon, Cordell, Heather J, Daly, Ann K. 2020. Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort☆. In Journal of hepatology, 73, 505-515. doi:10.1016/j.jhep.2020.04.003. https://pubmed.ncbi.nlm.nih.gov/32298765/
10. Chen, Yanhua, Du, Xiaomeng, Kuppa, Annapurna, Palmer, Nicholette D, Speliotes, Elizabeth K. 2023. Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease. In Nature genetics, 55, 1640-1650. doi:10.1038/s41588-023-01497-6. https://pubmed.ncbi.nlm.nih.gov/37709864/