Angptl3-KO 基因敲除小鼠

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产品名称

Angptl3-KO 基因敲除小鼠

产品编号

S-KO-09081

品系全称

C57BL/6NCya-Angptl3em1/Cya

品系背景

C57BL/6NCya

品系编号

KOCMP-30924-Angptl3-B6N-VA

品系状态

使用本品系发表的文献需注明: Angptl3-KO 基因敲除小鼠 mice (Strain S-KO-09081) 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
angiopoietin-like 3
基因别称
hypl
染色体号
Chr 4 (Mouse)
转录本 ID
NCBI: NM_013913 | Ensembl: ENSMUST00000030280
修饰方式
全身性基因敲除
靶向范围
Exon 1~5
敲除长度
~4.5 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:1353627Mice homozygous for a disruption in this gene display decreased plasma cholesterol and triglyceride levels. A spontaneous mutation results in a similar phenotype except that there is also a reduction in fat pad weight and decreased free fatty acid levels.

发表文献

Cell Reports
2022-09-26
Hepatic ER stress suppresses adipose browning through ATF4-CIRP-ANGPTL3 cascade
1
ANGPTL3,也称为Angiopoietin-like 3,是一种在人类脂质代谢中发挥重要作用的基因。它编码的蛋白可以抑制脂蛋白脂肪酶(LPL)的活性,影响甘油三酯的水解。ANGPTL3的基因变异与脂质代谢紊乱相关,其功能缺失(loss-of-function, LOF)突变会导致一种称为家族性联合低脂血症(familial combined hypolipidemia)的疾病,患者血液中的脂质水平显著降低[1]。此外,ANGPTL3的过表达与动脉粥样硬化的进展相关,因为它可以直接调节斑块中巨噬细胞的激活[4]。

研究表明,ANGPTL3的基因变异与家族性高胆固醇血症(familial hypercholesterolemia, FH)患者的脂质水平有关。在家族性高胆固醇血症中,ANGPTL3的功能缺失突变与较低的甘油三酯、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平相关。这些变异还与动脉粥样硬化性心血管疾病的风险降低相关。在动物模型中,ANGPTL3的基因敲除可以显著降低血清中的ANGPTL3蛋白、LDL-C和甘油三酯水平[2]。此外,ANGPTL3的功能缺失突变在冠状动脉疾病患者中的频率低于对照组,这表明ANGPTL3的抑制可能对心血管疾病具有保护作用[3]。

针对ANGPTL3的治疗方法正在开发中,例如evinacumab,这是一种针对ANGPTL3的单克隆抗体。在临床试验中,evinacumab能够显著降低家族性高胆固醇血症患者的LDL-C水平,并且安全性良好[5]。除了单克隆抗体,antisense oligonucleotides和microRNA-27b(miR-27b)等药物也在研发中,以模仿ANGPTL3功能缺失突变的效果[6]。

ANGPTL3的功能抑制为治疗家族性高胆固醇血症和其他脂质代谢紊乱提供了新的策略。未来的研究可能集中在开发更有效、更安全的ANGPTL3抑制剂,并探索其在其他心血管疾病中的应用。ANGPTL3的深入研究有助于我们更好地理解脂质代谢的调节机制,并为心血管疾病的治疗提供新的思路和策略[7,8,9]。

参考文献:
1. Bea, A M, Franco-Marín, E, Marco-Benedí, V, Civeira, F, Lamiquiz-Moneo, I. 2021. ANGPTL3 gene variants in subjects with familial combined hyperlipidemia. In Scientific reports, 11, 7002. doi:10.1038/s41598-021-86384-y. https://pubmed.ncbi.nlm.nih.gov/33772079/
2. Qiu, Min, Glass, Zachary, Chen, Jinjin, Zhang, Feng, Xu, Qiaobing. . Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2020401118. https://pubmed.ncbi.nlm.nih.gov/33649229/
3. Dewey, Frederick E, Gusarova, Viktoria, Dunbar, Richard L, Gromada, Jesper, Baras, Aris. 2017. Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease. In The New England journal of medicine, 377, 211-221. doi:10.1056/NEJMoa1612790. https://pubmed.ncbi.nlm.nih.gov/28538136/
4. Zhang, Yuejie, Yan, Cen, Dong, Yuan, Sun, Fenghui, Feng, Yingmei. 2024. ANGPTL3 accelerates atherosclerotic progression via direct regulation of M1 macrophage activation in plaque. In Journal of advanced research, , . doi:10.1016/j.jare.2024.05.011. https://pubmed.ncbi.nlm.nih.gov/38740260/
5. Raal, Frederick J, Rosenson, Robert S, Reeskamp, Laurens F, Zhang, Yi, Gaudet, Daniel. . Evinacumab for Homozygous Familial Hypercholesterolemia. In The New England journal of medicine, 383, 711-720. doi:10.1056/NEJMoa2004215. https://pubmed.ncbi.nlm.nih.gov/32813947/
6. Athyros, Vasilios G, Katsiki, Niki, Dimakopoulou, Aikaterini, Alataki, Sofia, Doumas, Michael. . Drugs that Mimic the Effect of Gene Mutations for the Prevention or the Treatment of Atherosclerotic Disease: From PCSK9 Inhibition to ANGPTL3 Inactivation. In Current pharmaceutical design, 24, 3638-3646. doi:10.2174/1381612824666181009100517. https://pubmed.ncbi.nlm.nih.gov/30306859/
7. Brandts, Julia, Ray, Kausik K. . Familial Hypercholesterolemia: JACC Focus Seminar 4/4. In Journal of the American College of Cardiology, 78, 1831-1843. doi:10.1016/j.jacc.2021.09.004. https://pubmed.ncbi.nlm.nih.gov/34711342/
8. Michaeli, Daniel Tobias, Michaeli, Julia Caroline, Albers, Sebastian, Boch, Tobias, Michaeli, Thomas. 2023. Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention. In American journal of cardiovascular drugs : drugs, devices, and other interventions, 23, 477-495. doi:10.1007/s40256-023-00594-5. https://pubmed.ncbi.nlm.nih.gov/37486464/
9. Bini, Simone, Tramontano, Daniele, Minicocci, Ilenia, D'Erasmo, Laura, Arca, Marcello. 2023. How ANGPTL3 Inhibition Will Help Our Clinical Practice? In Current atherosclerosis reports, 25, 19-29. doi:10.1007/s11883-022-01076-w. https://pubmed.ncbi.nlm.nih.gov/36607583/

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