Nr4a1-flox 基因敲除小鼠

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产品名称

Nr4a1-flox 基因敲除小鼠

产品编号

S-CKO-02913

品系全称

C57BL/6NCya-Nr4a1em1flox/Cya

品系背景

C57BL/6NCya

品系编号

CKOCMP-15370-Nr4a1-B6N-VA

品系状态

使用本品系发表的文献需注明: Nr4a1-flox 基因敲除小鼠 mice (Strain S-CKO-02913) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型
MAPK信号通路
PI3K-Akt信号通路
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 4, group A, member 1
基因别称
GFRP1,Gfrp,Hbr-1,Hbr1,Hmr,N10,NGFI-B,NGFIB,NP10,NUR77-1,NUR77-2,TIS1,TR3,nur77
染色体号
Chr 15 (Mouse)
转录本 ID
NCBI: NM_010444 | Ensembl: ENSMUST00000023779
修饰方式
条件性基因敲除
靶向范围
Exon 3~6
敲除长度
~2.0 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:1352454Mice homozygous for a targeted null mutation are viable, fertile, and display a normal HPA axis function, as well as normal thymic and peripheral T cell deletion. Homozygous KO decreases apoptosis and increases proliferation of B cell stimulated by a single antigen.

发表文献

Immunity
2024-09-22
Notch signaling regulates macrophage-mediated inflammation in metabolic dysfunction-associated steatotic liver disease
1
NR4A1,也称为Nur77,是核受体亚家族4A成员之一,是一种重要的转录因子。它能够结合DNA并调节基因表达,影响细胞分化和生理过程。NR4A1在多种生物学过程中发挥重要作用,包括细胞凋亡、炎症反应和肿瘤发生等。

NR4A1在T细胞功能中起着关键作用。一项研究发现,NR4A1在耐受性T细胞中稳定高表达,而过表达NR4A1会抑制效应T细胞分化,而NR4A1的缺失则会克服T细胞耐受性,增强效应功能,并提高对肿瘤和慢性病毒的抗性[1]。另一项研究发现,NR4A1在肿瘤微环境中的干细胞样CD8+ T细胞中高表达,NR4A1的过表达促进干细胞样T细胞的积累,而NR4A1的缺失则提高肿瘤控制效果[4]。

NR4A1在炎症反应中也发挥着重要作用。研究发现,NR4A1可以调节肠纤维化过程,并抑制炎症相关信号传导。NR4A1的缺失会导致肠纤维化加重,而NR4A1的激活可以减少TGF-β1诱导的胶原蛋白沉积和纤维化相关基因表达[2]。此外,NR4A1还可以通过非基因组效应影响细胞凋亡和自噬等过程[9]。

NR4A1在肿瘤发生中也起着重要作用。研究发现,NR4A1可以通过调节立即早期基因的表达来抑制肿瘤细胞的复制应激,而NR4A1的缺失会导致染色体不稳定和增殖失败[3]。此外,NR4A1还可以与FBW7协同作用,调节细胞凋亡和铁死亡等过程,从而影响肿瘤细胞的发生和发展[7]。

综上所述,NR4A1是一种重要的转录因子,在细胞凋亡、炎症反应和肿瘤发生等过程中发挥着重要作用。NR4A1的研究有助于深入理解其生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略[1,2,3,4,5,6,7,8,9,10]。

参考文献:
1. Liu, Xindong, Wang, Yun, Lu, Huiping, Bian, Xiu-Wu, Dong, Chen. 2019. Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction. In Nature, 567, 525-529. doi:10.1038/s41586-019-0979-8. https://pubmed.ncbi.nlm.nih.gov/30814730/
2. Pulakazhi Venu, Vivek Krishna, Alston, Laurie, Iftinca, Mircea, Altier, Christophe, Hirota, Simon A. 2021. Nr4A1 modulates inflammation-associated intestinal fibrosis and dampens fibrogenic signaling in myofibroblasts. In American journal of physiology. Gastrointestinal and liver physiology, 321, G280-G297. doi:10.1152/ajpgi.00338.2019. https://pubmed.ncbi.nlm.nih.gov/34288735/
3. Guo, Hongshan, Golczer, Gabriel, Wittner, Ben S, Lawrence, Michael S, Haber, Daniel A. . NR4A1 regulates expression of immediate early genes, suppressing replication stress in cancer. In Molecular cell, 81, 4041-4058.e15. doi:10.1016/j.molcel.2021.09.016. https://pubmed.ncbi.nlm.nih.gov/34624217/
4. Hao, Jing, Li, Ruifeng, Zhao, Xiaohong, Ni, Ling, Dong, Chen. 2024. NR4A1 transcriptionally regulates the differentiation of stem-like CD8+ T cells in the tumor microenvironment. In Cell reports, 43, 114301. doi:10.1016/j.celrep.2024.114301. https://pubmed.ncbi.nlm.nih.gov/38823016/
5. Li, Wei, Hang, Saiyu, Fang, Yuan, Devlin, A Sloan, Huh, Jun R. 2021. A bacterial bile acid metabolite modulates Treg activity through the nuclear hormone receptor NR4A1. In Cell host & microbe, 29, 1366-1377.e9. doi:10.1016/j.chom.2021.07.013. https://pubmed.ncbi.nlm.nih.gov/34416161/
6. Srirat, Tanakorn, Hayakawa, Taeko, Mise-Omata, Setsuko, Ito, Minako, Yoshimura, Akihiko. 2024. NR4a1/2 deletion promotes accumulation of TCF1+ stem-like precursors of exhausted CD8+ T cells in the tumor microenvironment. In Cell reports, 43, 113898. doi:10.1016/j.celrep.2024.113898. https://pubmed.ncbi.nlm.nih.gov/38451819/
7. Ye, Zeng, Zhuo, Qifeng, Hu, Qiangsheng, Yu, Xianjun, Ji, Shunrong. 2020. FBW7-NRA41-SCD1 axis synchronously regulates apoptosis and ferroptosis in pancreatic cancer cells. In Redox biology, 38, 101807. doi:10.1016/j.redox.2020.101807. https://pubmed.ncbi.nlm.nih.gov/33271455/
8. Jiang, Longying, Wei, Hudie, Yan, Ningning, Chen, Zhuchu, Chen, Yongheng. 2019. Structural basis of NR4A1 bound to the human pituitary proopiomelanocortin gene promoter. In Biochemical and biophysical research communications, 523, 1-5. doi:10.1016/j.bbrc.2019.11.192. https://pubmed.ncbi.nlm.nih.gov/31822342/
9. Pawlak, Alicja, Strzadala, Leon, Kalas, Wojciech. 2014. Non-genomic effects of the NR4A1/Nur77/TR3/NGFIB orphan nuclear receptor. In Steroids, 95, 1-6. doi:10.1016/j.steroids.2014.12.020. https://pubmed.ncbi.nlm.nih.gov/25555471/
10. Avagyan, S, Henninger, J E, Mannherz, W P, Moore, J L, Zon, L I. 2021. Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis. In Science (New York, N.Y.), 374, 768-772. doi:10.1126/science.aba9304. https://pubmed.ncbi.nlm.nih.gov/34735227/

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