Soat2-flox 基因敲除小鼠

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产品名称

Soat2-flox 基因敲除小鼠

产品编号

S-CKO-06682

品系全称

C57BL/6JCya-Soat2em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-223920-Soat2-B6J-VA

品系状态

使用本品系发表的文献需注明: Soat2-flox 基因敲除小鼠 mice (Strain S-CKO-06682) 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
sterol O-acyltransferase 2
基因别称
ACAT2,D15Wsu97e
染色体号
Chr 15 (Mouse)
转录本 ID
NCBI: NM_146064 | Ensembl: ENSMUST00000023806
修饰方式
条件性基因敲除
靶向范围
Exon 3~5
敲除长度
~2.1 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:1332226Homozygous mutant animals exhibit elevated serum triglyceride levels and are resistant to fatty liver, hyperlipidemia, and gallstone development when fed a high fat, high cholesterol diet. When fed a Western diet homozygous mutant animals exhibit elevated HDL levels.
Soat2,也称为酰基辅酶A:胆固醇酰基转移酶2(ACAT2),是一种重要的胆固醇酯化酶。胆固醇酯化是胆固醇代谢中的一个关键步骤,它涉及到将胆固醇与长链脂肪酸结合形成胆固醇酯。胆固醇酯不仅是胆固醇在体内运输的主要形式,也是细胞内胆固醇储存的主要形式。Soat2主要在肝脏和小肠中表达,负责将胆固醇转化为胆固醇酯,这些胆固醇酯随后被包装成脂蛋白,如低密度脂蛋白(LDL)和高密度脂蛋白(HDL),通过血液运输到全身各个部位。

Soat2的活性在胆固醇代谢和脂质稳态中发挥着重要作用。在胚胎发育过程中,Soat2参与卵黄胆固醇的转运,对胚胎的发育至关重要[1]。在成年动物中,Soat2的活性与胆固醇酯的生成和储存有关,这些胆固醇酯在维持细胞内胆固醇平衡和脂质代谢中起着关键作用。

Soat2的功能失调与多种疾病的发生和发展有关。例如,Soat2的活性增强会导致胆固醇酯的过度积累,增加动脉粥样硬化的风险[2]。此外,Soat2的活性还与肝脏疾病、如脂肪肝的发生有关[7]。研究表明,通过抑制Soat2的活性可以稳定动脉粥样硬化斑块,减少肝脏胆固醇酯的积累,从而改善相关疾病的治疗效果[4,5]。

Soat2的表达受到多种因素的调控。例如,甲状腺激素可以通过诱导miRNA-181d的表达来负调节Soat2的mRNA表达[3]。此外,LXR(肝X受体)也参与Soat2的调控,LXR的激活可以增加Soat2的表达,而LXR的抑制则可以降低Soat2的表达[6]。这些调控机制为Soat2功能的调节提供了新的思路,也为相关疾病的治疗提供了潜在的治疗靶点。

综上所述,Soat2是一种重要的胆固醇酯化酶,在胆固醇代谢和脂质稳态中发挥着重要作用。Soat2的功能失调与多种疾病的发生和发展有关,如动脉粥样硬化、肝脏疾病等。Soat2的表达受到多种因素的调控,这些调控机制为Soat2功能的调节提供了新的思路,也为相关疾病的治疗提供了潜在的治疗靶点。进一步研究Soat2的功能和调控机制,将有助于我们更好地理解胆固醇代谢和脂质稳态的调控机制,为相关疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Chang, Nai-Yun, Chan, Yen-Ju, Ding, Shih-Torng, HuangFu, Wei-Chun, Liu, I-Hsuan. 2016. Sterol O-Acyltransferase 2 Contributes to the Yolk Cholesterol Trafficking during Zebrafish Embryogenesis. In PloS one, 11, e0167644. doi:10.1371/journal.pone.0167644. https://pubmed.ncbi.nlm.nih.gov/27936201/
2. Zhang, Jun, Sawyer, Janet K, Marshall, Stephanie M, Brown, J Mark, Rudel, Lawrence L. 2014. Cholesterol esters (CE) derived from hepatic sterol O-acyltransferase 2 (SOAT2) are associated with more atherosclerosis than CE from intestinal SOAT2. In Circulation research, 115, 826-33. doi:10.1161/CIRCRESAHA.115.304378. https://pubmed.ncbi.nlm.nih.gov/25239141/
3. Yap, Chui Sun, Sinha, Rohit Anthony, Ota, Sho, Katsuki, Masahito, Yen, Paul Michael. 2013. Thyroid hormone negatively regulates CDX2 and SOAT2 mRNA expression via induction of miRNA-181d in hepatic cells. In Biochemical and biophysical research communications, 440, 635-9. doi:10.1016/j.bbrc.2013.09.116. https://pubmed.ncbi.nlm.nih.gov/24103759/
4. Melchior, John T, Olson, John D, Kelley, Kathryn L, Link, Kerry M, Rudel, Lawrence L. 2015. Targeted Knockdown of Hepatic SOAT2 With Antisense Oligonucleotides Stabilizes Atherosclerotic Plaque in ApoB100-only LDLr-/- Mice. In Arteriosclerosis, thrombosis, and vascular biology, 35, 1920-7. doi:10.1161/ATVBAHA.115.305747. https://pubmed.ncbi.nlm.nih.gov/26229140/
5. Lopez, Adam M, Posey, Kenneth S, Turley, Stephen D. 2014. Deletion of sterol O-acyltransferase 2 (SOAT2) function in mice deficient in lysosomal acid lipase (LAL) dramatically reduces esterified cholesterol sequestration in the small intestine and liver. In Biochemical and biophysical research communications, 454, 162-6. doi:10.1016/j.bbrc.2014.10.063. https://pubmed.ncbi.nlm.nih.gov/25450374/
6. Griffett, Kristine, Hayes, Matthew, Bedia-Diaz, Gonzalo, Elgendy, Bahaa, Burris, Thomas P. 2022. Antihyperlipidemic Activity of Gut-Restricted LXR Inverse Agonists. In ACS chemical biology, 17, 1143-1154. doi:10.1021/acschembio.2c00057. https://pubmed.ncbi.nlm.nih.gov/35417135/
7. Ahmed, O, Pramfalk, C, Pedrelli, M, Eriksson, M, Parini, P. 2018. Genetic depletion of Soat2 diminishes hepatic steatosis via genes regulating de novo lipogenesis and by GLUT2 protein in female mice. In Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 51, 1016-1022. doi:10.1016/j.dld.2018.12.007. https://pubmed.ncbi.nlm.nih.gov/30630736/