Nr1h3-KO 基因敲除小鼠

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产品名称

Nr1h3-KO 基因敲除小鼠

产品编号

S-KO-05649

品系全称

C57BL/6NCya-Nr1h3em1/Cya

品系背景

C57BL/6NCya

品系编号

KOCMP-22259-Nr1h3-B6N-VA

品系状态

使用本品系发表的文献需注明: Nr1h3-KO 基因敲除小鼠 mice (Strain S-KO-05649) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
KO小鼠库模型
核受体Brite

基本信息

基因研究概述

质控标准

基因
基因全称
nuclear receptor subfamily 1, group H, member 3
基因别称
LXR,RLD1,Unr1
染色体号
Chr 2 (Mouse)
转录本 ID
NCBI: NM_013839 | Ensembl: ENSMUST00000111356
修饰方式
全身性基因敲除
靶向范围
Exon 3~7
敲除长度
~2.6 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:1352462Mice homozygous for a knock-out allele exhibit decreased male fertility, increased suseceptibility to bacterial infection, and diet-sensitive increase in liver size, steatosis, and cholesterol level.
NR1H3,也称为肝脏X受体α(LXRα),是一种重要的核激素受体。NR1H3在调节脂质和脂肪酸的积累中起着关键作用,影响肝脏、脂肪组织和骨骼肌的功能。NR1H3的表达水平与脂质沉积能力相关,其基因多态性可能影响个体的脂质代谢和肥胖风险[2]。此外,NR1H3在多种疾病中发挥重要作用,包括动脉粥样硬化、糖尿病、乳腺癌和系统性红斑狼疮等。

在动脉粥样硬化中,NR1H3的表达水平升高,可能促进动脉瘤的形成。研究发现,NR1H3通过UHRF1的表观遗传修饰,影响miR-26b-3p的表达,进而影响细胞外基质降解、炎症和血管平滑肌细胞表型转换,从而促进动脉瘤的形成[1]。此外,NR1H3的表达与巨噬细胞浸润和乳腺癌患者的预后相关。研究发现,NR1H3的表达在乳腺癌组织中显著降低,与肿瘤浸润免疫细胞的浸润水平密切相关,且NR1H3的表达和巨噬细胞浸润水平是乳腺癌的独立预后因素[3]。NR1H3的表达与系统性红斑狼疮的易感性相关。研究发现,NR1H3基因启动子区域的单核苷酸多态性(SNPs)与系统性红斑狼疮的易感性相关,其中NR1H3基因启动子区域的-1830 T>C多态性可能与NR1H3的表达调节相关[4]。

NR1H3的表达与家族性多发性硬化症的发病相关。研究发现,NR1H3基因中的p.Arg415Gln突变与家族性多发性硬化症的发病相关,且NR1H3基因中的常见变异rs2279238与进展性多发性硬化症的风险增加相关[5]。NR1H3的表达与子宫内膜癌的发生和发展相关。研究发现,NR1H3在子宫内膜癌组织中表达上调,且NR1H3的表达抑制子宫内膜癌细胞增殖,可能成为子宫内膜癌的潜在治疗靶点[6]。NR1H3的表达与弥漫性大B细胞淋巴瘤的预后相关。研究发现,NR1H3的表达在弥漫性大B细胞淋巴瘤组织中与肿瘤微环境相关,且NR1H3高表达患者的生存期较长[7]。

NR1H3的表达与高血压患者的降压药物反应相关。研究发现,NR1H3基因启动子区域的rs11039149A>G变异与高血压患者对钙通道阻滞剂(CCBs)单药治疗的收缩压变化相关,携带rs11039149AG基因型的患者与AA基因型患者相比,收缩压升高更明显[8]。

综上所述,NR1H3在多种疾病中发挥重要作用,包括动脉粥样硬化、糖尿病、乳腺癌、系统性红斑狼疮、家族性多发性硬化症、子宫内膜癌和弥漫性大B细胞淋巴瘤等。NR1H3的表达与疾病的易感性和预后相关,可能成为疾病诊断、治疗和预后的重要生物标志物。

参考文献:
1. Guo, Xiao, Zhong, Jianmei, Zhao, Yichao, Chen, Alex F, Pu, Jun. 2024. LXRα Promotes Abdominal Aortic Aneurysm Formation Through UHRF1 Epigenetic Modification of miR-26b-3p. In Circulation, 150, 30-46. doi:10.1161/CIRCULATIONAHA.123.065202. https://pubmed.ncbi.nlm.nih.gov/38557060/
2. Zhang, Bo, Shang, Peng, Qiangba, Yangzong, Wang, Zhixiu, Zhang, Hao. 2016. The association of NR1H3 gene with lipid deposition in the pig. In Lipids in health and disease, 15, 99. doi:10.1186/s12944-016-0269-5. https://pubmed.ncbi.nlm.nih.gov/27229308/
3. Zhang, Jing, Zhang, Jiawen, Zhao, Weiwei, Li, Qingxian, Cheng, Wenwu. 2023. Low expression of NR1H3 correlates with macrophage infiltration and indicates worse survival in breast cancer. In Frontiers in genetics, 13, 1067826. doi:10.3389/fgene.2022.1067826. https://pubmed.ncbi.nlm.nih.gov/36699456/
4. Jeon, Ja-Young, Nam, Jin-Young, Kim, Hyoun-Ah, Bae, Sang-Cheol, Suh, Chang-Hee. 2014. Liver X receptors alpha gene (NR1H3) promoter polymorphisms are associated with systemic lupus erythematosus in Koreans. In Arthritis research & therapy, 16, R112. doi:10.1186/ar4563. https://pubmed.ncbi.nlm.nih.gov/24886807/
5. Wang, Zhe, Sadovnick, A Dessa, Traboulsee, Anthony L, Song, Weihong, Vilariño-Güell, Carles. . Nuclear Receptor NR1H3 in Familial Multiple Sclerosis. In Neuron, 90, 948-54. doi:10.1016/j.neuron.2016.04.039. https://pubmed.ncbi.nlm.nih.gov/27253448/
6. Fang, Fang, Li, Dawei, Zhao, Lu, Zhang, Teng, Cui, Baoxia. 2019. Expression of NR1H3 in endometrial carcinoma and its effect on the proliferation of Ishikawa cells in vitro. In OncoTargets and therapy, 12, 685-697. doi:10.2147/OTT.S180534. https://pubmed.ncbi.nlm.nih.gov/30705597/
7. Vegliante, Maria Carmela, Mazzara, Saveria, Zaccaria, Gian Maria, Pileri, Stefano A, Ciavarella, Sabino. 2022. NR1H3 (LXRα) is associated with pro-inflammatory macrophages, predicts survival and suggests potential therapeutic rationales in diffuse large b-cell lymphoma. In Hematological oncology, 40, 864-875. doi:10.1002/hon.3050. https://pubmed.ncbi.nlm.nih.gov/35850118/
8. Chen, Yu, Han, Yuqing, Wu, Yiyi, Zhang, Shuyuan, Zhang, Weili. 2023. Pharmacogenetic association of the NR1H3 promoter variant with antihypertensive response among patients with hypertension: A longitudinal study. In Frontiers in pharmacology, 14, 1083134. doi:10.3389/fphar.2023.1083134. https://pubmed.ncbi.nlm.nih.gov/36950018/