Ccr7-KO 基因敲除小鼠

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产品名称

Ccr7-KO 基因敲除小鼠

产品编号

S-KO-01548

品系全称

C57BL/6JCya-Ccr7em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-12775-Ccr7-B6J-VA

品系状态

使用本品系发表的文献需注明: Ccr7-KO 基因敲除小鼠 mice (Strain S-KO-01548) 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
C-C motif chemokine receptor 7
基因别称
CC-CKR-7,CCR-7,CD197,Cdw197,Cmkbr7,EBI1,Ebi1h
染色体号
Chr 11 (Mouse)
转录本 ID
NCBI: NM_007719 | Ensembl: ENSMUST00000103134
修饰方式
全身性基因敲除
靶向范围
Exon 3
敲除长度
~3.0 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:103011Homozygous mice exhibit an impaired primary immune response. Dendritic cells, B, T and T regulatory cells show impaired migration to the lymph nodes and secondary lymph organs exhibit morphological abnormalities. Lymphocytic infiltrates to the pancreas, lung and stomach are observed in aged mice.
CCR7,也称为C-C趋化因子受体7,是一种属于G蛋白偶联受体家族的细胞表面受体。它在多种免疫细胞上表达,包括未成熟的T细胞、B细胞和树突状细胞(DCs)。CCR7主要与CCL19和CCL21两种趋化因子结合,这两种趋化因子在淋巴组织和次级淋巴器官中高度表达。CCR7/CCL19/21轴在淋巴细胞归巢到淋巴结和派尔斑等淋巴组织结构中起着至关重要的作用,这对于启动保护性免疫和维持免疫稳态至关重要。

CCR7的表达和功能受到多种因素的调控。例如,研究显示,转录因子PU.1(也称为Spi1)通过与CCR7基因启动子区的结合,正调节CCR7在未成熟的CD4+ T细胞中的表达。在未成熟的CD4+ T细胞中,PU.1的缺失会导致CCR7表达水平的降低[3]。此外,CCR7的激活可以诱导长非编码RNA lnc-Dpf3的表达。lnc-Dpf3通过直接与HIF-1α结合,抑制HIF-1α依赖性糖酵解基因Ldha的转录,从而抑制DC的糖酵解代谢和迁移能力[1]。

CCR7在多种疾病中发挥着重要作用。在口腔鳞状细胞癌(OSCC)中,CCR7的敲除可以显著抑制肿瘤生长。单细胞RNA测序结果显示,CCR7基因敲除组的肿瘤细胞比例较低,但炎症细胞的比例显著高于野生型组。CCR7可以促进M2巨噬细胞极化,从而促进OSCC细胞的增殖、侵袭和迁移[2]。在糖尿病足溃疡(DFU)和周围动脉疾病(PAD)中,CCR7基因表达上调,并与疾病的发生和发展密切相关[4]。此外,CCR7和CD6基因的表达水平在颅内动脉瘤(IA)患者中显著升高,并且与IA破裂风险相关[5]。

CCR7在肿瘤相关成纤维细胞(CAFs)中也发挥着重要作用。在TNBC中,CCR7是CAFs的一个重要标记基因,并且与肿瘤的预后和治疗价值相关[6]。在斑马鱼早期胚胎发育过程中,CCR7基因的突变会影响形态发生和细胞分化过程[7]。在鱼类中,CCR7基因在免疫细胞中表达,并在病毒和寄生虫感染过程中发挥重要作用[8]。

CCR7基因的突变与成人T细胞白血病/淋巴瘤(ATL)患者对mogamulizumab治疗的反应相关。在mogamulizumab治疗的患者中,CCR7基因的突变与较差的生存率相关[9]。此外,CCR7在乳腺癌进展中也发挥着重要作用。CCR7/CCL19/21轴可以诱导乳腺癌细胞的增殖和迁移,从而促进肿瘤的生长和转移[10]。

综上所述,CCR7在免疫细胞归巢、肿瘤生长和转移、以及多种疾病的发生和发展中发挥着重要作用。CCR7的表达和功能受到多种因素的调控,包括转录因子和长非编码RNA。CCR7基因的突变与多种疾病的不良预后相关,这为疾病的诊断和治疗提供了新的思路和策略。

参考文献:
1. Liu, Juan, Zhang, Xiaomin, Chen, Kun, Li, Zhiqing, Cao, Xuetao. 2019. CCR7 Chemokine Receptor-Inducible lnc-Dpf3 Restrains Dendritic Cell Migration by Inhibiting HIF-1α-Mediated Glycolysis. In Immunity, 50, 600-615.e15. doi:10.1016/j.immuni.2019.01.021. https://pubmed.ncbi.nlm.nih.gov/30824325/
2. Wang, Zengxu, Kirkwood, Keith L, Wang, Yao, Sun, Changfu, Liu, Fayu. 2024. Analysis of the effect of CCR7 on the microenvironment of mouse oral squamous cell carcinoma by single-cell RNA sequencing technology. In Journal of experimental & clinical cancer research : CR, 43, 94. doi:10.1186/s13046-024-03013-y. https://pubmed.ncbi.nlm.nih.gov/38539232/
3. Yashiro, Takuya, Takeuchi, Hiromi, Kasakura, Kazumi, Nishiyama, Chiharu. 2020. PU.1 regulates Ccr7 gene expression by binding to its promoter in naïve CD4+ T cells. In FEBS open bio, 10, 1115-1121. doi:10.1002/2211-5463.12861. https://pubmed.ncbi.nlm.nih.gov/32297481/
4. Zou, Jie, Zhang, Wen, Chen, Xiaoming, Su, Wenxing, Yu, Daojiang. 2022. Data mining reveal the association between diabetic foot ulcer and peripheral artery disease. In Frontiers in public health, 10, 963426. doi:10.3389/fpubh.2022.963426. https://pubmed.ncbi.nlm.nih.gov/36062083/
5. Xu, Dan-Dan, Liu, Xiao-Qiang, Wu, Zhi-Sheng. . CD6 and CCR7 as Genetic Biomarkers in Evaluating Intracranial Aneurysm Rupture Risk. In Journal of integrative neuroscience, 23, 55. doi:10.31083/j.jin2303055. https://pubmed.ncbi.nlm.nih.gov/38538213/
6. Wu, Xiaoqing, Lu, Wenping, Zhang, Weixuan, Cui, Yongjia, Zhuo, Zhili. 2023. Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels the heterogeneity of cancer-associated fibroblasts in TNBC. In Aging, 15, 12674-12697. doi:10.18632/aging.205205. https://pubmed.ncbi.nlm.nih.gov/37963845/
7. Goto, Toshiyasu, Michiue, Tatsuo, Shibuya, Hiroshi. 2022. ccr7 affects both morphogenesis and differentiation during early Xenopus embryogenesis. In Development, growth & differentiation, 64, 254-260. doi:10.1111/dgd.12790. https://pubmed.ncbi.nlm.nih.gov/35581152/
8. Ordás, M Camino, Castro, Rosario, Dixon, Brian, Cuesta, Alberto, Tafalla, Carolina. 2012. Identification of a novel CCR7 gene in rainbow trout with differential expression in the context of mucosal or systemic infection. In Developmental and comparative immunology, 38, 302-11. doi:10.1016/j.dci.2012.07.001. https://pubmed.ncbi.nlm.nih.gov/22858409/
9. Sakamoto, Yuma, Ishida, Takashi, Masaki, Ayako, Ueda, Ryuzo, Inagaki, Hiroshi. 2022. CCR7 alterations associated with inferior outcome of adult T-cell leukemia/lymphoma under mogamulizumab treatment. In Hematological oncology, 40, 876-884. doi:10.1002/hon.3072. https://pubmed.ncbi.nlm.nih.gov/36043457/
10. Rizeq, Balsam, Malki, Mohammed Imad. 2020. The Role of CCL21/CCR7 Chemokine Axis in Breast Cancer Progression. In Cancers, 12, . doi:10.3390/cancers12041036. https://pubmed.ncbi.nlm.nih.gov/32340161/