Ffar2-KO 基因敲除小鼠

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产品名称

Ffar2-KO 基因敲除小鼠

产品编号

S-KO-06605

品系全称

C57BL/6NCya-Ffar2em1/Cya

品系背景

C57BL/6NCya

品系编号

KOCMP-233079-Ffar2-B6N-VA

品系状态

使用本品系发表的文献需注明: Ffar2-KO 基因敲除小鼠 mice (Strain S-KO-06605) 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
free fatty acid receptor 2
基因别称
GPCR43,Gpr43
染色体号
Chr 7 (Mouse)
转录本 ID
NCBI: NM_146187 | Ensembl: ENSMUST00000053156
修饰方式
全身性基因敲除
靶向范围
Exon 3
敲除长度
~1.8 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:2441731Mice homozygous for a null allele show altered granulocyte and neutrophil physiology and increased inflammation in models of induced colitis, arthritis and asthma, whereas homozygotes for a different null allele show reduced neutrophil recruitment and decreased susceptibility to induced colitis.

发表文献

The ISME Journal
2023-11-09
Ginsenoside Rg3 enriches SCFA-producing commensal bacteria to confer protection against enteric viral infection via the cGAS-STING-type I IFN axis
Nature Communications
2023-02
Microbiota-derived acetate enhances host antiviral response via NLRP3
1
Ffar2,也称为游离脂肪酸受体2(Free Fatty Acid Receptor 2),是一种G蛋白偶联受体(G-protein coupled receptor, GPCR),在人体中主要表达于免疫细胞和肠道上皮细胞。FFAR2对短链脂肪酸(Short-chain fatty acids, SCFAs)如乙酸、丙酸和丁酸有高度的亲和力,这些SCFAs是肠道微生物群在发酵不可消化纤维时产生的代谢物[8]。FFAR2的激活能够调节多种生物学过程,包括免疫反应、肠道稳态、能量代谢和神经功能[1,2,3,4,5,6,7,8,9,10]。

在免疫系统中,FFAR2的表达与免疫抑制细胞的活化密切相关。例如,在肺癌患者中,FFAR2在骨髓源性抑制细胞(Myeloid-derived suppressor cells, MDSCs)中高表达,而MDSCs是已知的免疫抑制细胞,与癌症患者的预后不良有关[1]。FFAR2的激活能够增强MDSCs的免疫抑制功能,促进肿瘤免疫逃逸。研究发现,在MDSCs中敲除Ffar2基因能够显著抑制肺腺癌的发生和发展,减少MDSCs的数量,并增加CD8+ T细胞的浸润,从而改善肿瘤免疫微环境[1]。

除了在免疫系统中的作用,FFAR2还在肠道免疫中发挥重要作用。在结肠固有层中,FFAR2的表达与第3组固有淋巴细胞(Group 3 innate lymphoid cells, ILC3s)的活化和功能有关[2]。FFAR2的激活能够促进ILC3s的增殖和功能,并增加ILC3s产生的IL-22水平,从而维持肠道上皮细胞的完整性和功能,以及防御病原体感染[2]。

此外,FFAR2还与肠道微生物群-大脑-行为轴(Microbiota-gut-brain axis)有关。研究发现,SCFAs能够调节大脑功能和行为,而FFAR2是SCFAs的主要受体之一[3,5]。SCFAs通过FFAR2激活下游信号通路,如AKT和ERK信号通路,进而影响神经递质和激素的释放,以及神经细胞的生长和分化[3]。

FFAR2还参与能量代谢的调节。研究表明,FFAR2的激活能够抑制脂肪细胞的分化和脂质的积累,并促进脂肪细胞的能量消耗[8]。此外,FFAR2还与糖尿病肾病的发生和发展有关,FFAR2的激活能够减少肾脏炎症和纤维化,保护肾脏功能[7]。

综上所述,FFAR2是一种重要的G蛋白偶联受体,在免疫调节、肠道稳态、能量代谢和神经功能中发挥重要作用。FFAR2的激活能够促进免疫抑制、肠道免疫、神经递质和激素的释放,以及脂肪细胞的能量消耗。FFAR2的研究有助于深入理解FFAR2的生物学功能及其在多种疾病中的作用机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Zhao, Zeda, Qin, Juliang, Qian, Ying, Liu, Mingyao, Du, Bing. 2024. FFAR2 expressing myeloid-derived suppressor cells drive cancer immunoevasion. In Journal of hematology & oncology, 17, 9. doi:10.1186/s13045-024-01529-6. https://pubmed.ncbi.nlm.nih.gov/38402237/
2. Chun, Eunyoung, Lavoie, Sydney, Fonseca-Pereira, Diogo, Layden, Brian T, Garrett, Wendy S. 2019. Metabolite-Sensing Receptor Ffar2 Regulates Colonic Group 3 Innate Lymphoid Cells and Gut Immunity. In Immunity, 51, 871-884.e6. doi:10.1016/j.immuni.2019.09.014. https://pubmed.ncbi.nlm.nih.gov/31628054/
3. Stilling, Roman M, van de Wouw, Marcel, Clarke, Gerard, Dinan, Timothy G, Cryan, John F. 2016. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? In Neurochemistry international, 99, 110-132. doi:10.1016/j.neuint.2016.06.011. https://pubmed.ncbi.nlm.nih.gov/27346602/
4. Liu, Qing, Tian, Xiaoli, Maruyama, Daisuke, Arjomandi, Mehrdad, Prakash, Arun. 2021. Lung immune tone via gut-lung axis: gut-derived LPS and short-chain fatty acids' immunometabolic regulation of lung IL-1β, FFAR2, and FFAR3 expression. In American journal of physiology. Lung cellular and molecular physiology, 321, L65-L78. doi:10.1152/ajplung.00421.2020. https://pubmed.ncbi.nlm.nih.gov/33851870/
5. van de Wouw, Marcel, Boehme, Marcus, Lyte, Joshua M, Dinan, Timothy G, Cryan, John F. 2018. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations. In The Journal of physiology, 596, 4923-4944. doi:10.1113/JP276431. https://pubmed.ncbi.nlm.nih.gov/30066368/
6. Buchynskyi, Mykhailo, Oksenych, Valentyn, Kamyshna, Iryna, Halabitska, Iryna, Kamyshnyi, Oleksandr. 2024. Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in Metabolic-Associated Fatty Liver Disease and COVID-19 Outcomes. In Viruses, 16, . doi:10.3390/v16060985. https://pubmed.ncbi.nlm.nih.gov/38932276/
7. Li, Yan Jun, Chen, Xiaochen, Kwan, Tony K, Chadban, Steven J, Wu, Huiling. 2020. Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid-Mediated Activation of G Protein-Coupled Receptors GPR43 and GPR109A. In Journal of the American Society of Nephrology : JASN, 31, 1267-1281. doi:10.1681/ASN.2019101029. https://pubmed.ncbi.nlm.nih.gov/32358041/
8. Mohammad, Sameer. . Role of Free Fatty Acid Receptor 2 (FFAR2) in the Regulation of Metabolic Homeostasis. In Current drug targets, 16, 771-5. doi:. https://pubmed.ncbi.nlm.nih.gov/25850624/
9. Orji, Oliver C, López-Domínguez, Maria B, Sandoval-Plata, Gabriela, Morgan, Kevin, Abhishek, Abhishek. . Upregulated expression of FFAR2 and SOC3 genes is associated with gout. In Rheumatology (Oxford, England), 62, 977-983. doi:10.1093/rheumatology/keac360. https://pubmed.ncbi.nlm.nih.gov/35731142/
10. Zou, Jun, Chassaing, Benoit, Singh, Vishal, Kumar, Matam Vijay, Gewirtz, Andrew T. 2017. Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health. In Cell host & microbe, 23, 41-53.e4. doi:10.1016/j.chom.2017.11.003. https://pubmed.ncbi.nlm.nih.gov/29276170/

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