Ikzf3-flox 基因敲除小鼠

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产品名称

Ikzf3-flox 基因敲除小鼠

产品编号

S-CKO-07126

品系全称

C57BL/6NCya-Ikzf3em1flox/Cya

品系背景

C57BL/6NCya

品系编号

CKOCMP-22780-Ikzf3-B6N-VA

品系状态

使用本品系发表的文献需注明: Ikzf3-flox 基因敲除小鼠 mice (Strain S-CKO-07126) 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
IKAROS family zinc finger 3
基因别称
5830411O07Rik,Aiolos,Zfpn1a3,Znfn1a3
染色体号
Chr 11 (Mouse)
转录本 ID
NCBI: NM_011771 | Ensembl: ENSMUST00000103141
修饰方式
条件性基因敲除
靶向范围
Exon 4~6
敲除长度
~5.5 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:1342542Homozygous mutants exhibit greatly reduced B cell populations in the peritoneum, marginal zone and recirculating bone marrow. Aging mutants express autoantibodies, frequently develop B cell lymphomas, and display symptoms characteristic of SLE.
IKZF3,也称为Aiolos,是一种重要的转录因子,属于IKAROS家族。IKAROS家族成员在免疫系统中的发育和功能调控中起着关键作用,尤其是在B淋巴细胞和T淋巴细胞的分化和成熟过程中。IKZF3蛋白具有锌指结构域,可以识别并结合特定的DNA序列,从而调控基因的表达。在B淋巴细胞中,IKZF3参与调节B细胞受体(BCR)信号通路,并影响B淋巴细胞的增殖、分化和存活。在T淋巴细胞中,IKZF3与Foxp3相互作用,参与调节调节性T细胞(Treg)的功能,从而影响免疫系统的稳态和自身免疫性疾病的发生。IKZF3的异常表达或突变与多种免疫相关疾病和癌症的发生发展密切相关。

研究表明,IKZF3在Treg细胞中与Foxp3相互作用,通过染色质重塑竞争性结合目标基因位点,抑制基因表达,从而限制自身免疫性疾病和抗肿瘤免疫[1]。IKZF3的缺失会导致Treg细胞功能受损,引发系统性自身免疫性疾病[1]。此外,IKZF3在急性淋巴母细胞白血病(ALL)中发生基因扩增,与ALL的发生发展密切相关[2]。IKZF3的缺失或突变会导致B细胞功能异常,增加B细胞淋巴瘤的风险[3]。IKZF3的突变还与系统性红斑狼疮(SLE)的发生发展相关[5],以及与Graves病的发生发展相关[8]。此外,IKZF3的扩增在HER2阳性乳腺癌中频繁发生,并且与HER2阳性乳腺癌的预后不良相关[6]。IKZF3的突变会影响其与DNA的结合特异性,进而影响STAT5的结合和基因表达[4]。IKZF3还与CD4+ T细胞中IL-10的表达相关,但并非IL-10表达的充分条件[7]。

综上所述,IKZF3是一种重要的转录因子,在免疫系统发育和功能调控中发挥重要作用。IKZF3的异常表达或突变与多种免疫相关疾病和癌症的发生发展密切相关。深入研究IKZF3的功能和调控机制,有助于揭示免疫相关疾病和癌症的发生发展机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Ichiyama, Kenji, Long, Jia, Kobayashi, Yusuke, Georgopoulos, Katia, Sakaguchi, Shimon. 2024. Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity. In Immunity, 57, 2043-2060.e10. doi:10.1016/j.immuni.2024.07.010. https://pubmed.ncbi.nlm.nih.gov/39111316/
2. Holmfeldt, Linda, Wei, Lei, Diaz-Flores, Ernesto, Loh, Mignon L, Mullighan, Charles G. 2013. The genomic landscape of hypodiploid acute lymphoblastic leukemia. In Nature genetics, 45, 242-52. doi:10.1038/ng.2532. https://pubmed.ncbi.nlm.nih.gov/23334668/
3. Montoya, Skye, Bourcier, Jessie, Noviski, Mark, Abdel-Wahab, Omar, Taylor, Justin. 2024. Kinase-impaired BTK mutations are susceptible to clinical-stage BTK and IKZF1/3 degrader NX-2127. In Science (New York, N.Y.), 383, eadi5798. doi:10.1126/science.adi5798. https://pubmed.ncbi.nlm.nih.gov/38301010/
4. Rodrigues de Oliveira, Bruno, Iansavitchous, James, Rysan, Heidi, Zorzi, Alexandra P, DeKoter, Rodney P. 2024. IKZF3/Aiolos H195Y mutation identified in a mouse model of B cell leukemia results in altered DNA binding and altered STAT5-dependent gene expression. In Gene, 900, 148131. doi:10.1016/j.gene.2024.148131. https://pubmed.ncbi.nlm.nih.gov/38216003/
5. Cai, Xinze, Qiao, Ying, Diao, Cheng, Chen, Dong, Jiang, Yi. 2014. Association between polymorphisms of the IKZF3 gene and systemic lupus erythematosus in a Chinese Han population. In PloS one, 9, e108661. doi:10.1371/journal.pone.0108661. https://pubmed.ncbi.nlm.nih.gov/25271777/
6. Lin, Chih-Yi, Yu, Chung-Jen, Shen, Chia-I, Tseng, Ling-Ming, Lai, Jiun-I. 2022. IKZF3 amplification frequently occurs in HER2-positive breast cancer and is a potential therapeutic target. In Medical oncology (Northwood, London, England), 39, 242. doi:10.1007/s12032-022-01812-x. https://pubmed.ncbi.nlm.nih.gov/36180600/
7. Ridley, Michael L, Fleskens, Veerle, Roberts, Ceri A, Lavender, Paul, Taams, Leonie S. 2020. IKZF3/Aiolos Is Associated with but Not Sufficient for the Expression of IL-10 by CD4+ T Cells. In Journal of immunology (Baltimore, Md. : 1950), 204, 2940-2948. doi:10.4049/jimmunol.1901283. https://pubmed.ncbi.nlm.nih.gov/32321757/
8. Li, Ling, Ding, Xiaolian, Wang, Xuan, Zhang, Jin-An, Sun, Peilong. 2018. Polymorphisms of IKZF3 Gene and Autoimmune Thyroid Diseases: Associated with Graves' Disease but Not with Hashimoto's Thyroiditis. In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 45, 1787-1796. doi:10.1159/000487870. https://pubmed.ncbi.nlm.nih.gov/29510406/