Fez1-KO 基因敲除小鼠

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产品名称

Fez1-KO 基因敲除小鼠

产品编号

S-KO-16801

品系全称

C57BL/6JCya-Fez1em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-235180-Fez1-B6J-VB

品系状态

使用本品系发表的文献需注明: Fez1-KO 基因敲除小鼠 mice (Strain S-KO-16801) 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
fasciculation and elongation protein zeta 1
基因别称
UNC-76,UNC76
染色体号
Chr 9 (Mouse)
转录本 ID
NCBI: NM_183171 | Ensembl: ENSMUST00000034630
修饰方式
全身性基因敲除
靶向范围
Exon 3
敲除长度
~2.1 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:2670976Mice homozygous for a null allele exhibit hyperactivity and increased sensitivity to methamphetamine.
FEZ1,全称为fasciculation and elongation protein zeta-1,是一种多功能性kinesin适配器蛋白,参与从神经退行性疾病到逆转录病毒和聚瘤病毒感染等多种生物过程。FEZ1在细胞内运输、转录调控、神经发育以及免疫反应等方面发挥着重要作用。FEZ1蛋白包含一个kinesin调节结构域,该结构域中的S58位点磷酸化对FEZ1的功能有重要调控作用[1]。

FEZ1在神经发育过程中具有重要作用,特别是在人脑发育早期。研究表明,FEZ1在胎儿大脑皮层中高度表达,并在神经发生过程中调节神经元祖细胞的分化和迁移[4]。FEZ1的缺失会影响神经元轴突和树突的发育,并显著延迟突触蛋白向发育中的神经突的运输,导致运动神经元发育缺陷[3]。此外,FEZ1还与精神分裂症的发病机制有关,其表达异常可能与该疾病的发生发展相关[2][7][8]。

FEZ1在免疫反应中也发挥着重要作用。研究表明,FEZ1的磷酸化可以调节热休克蛋白8(HSPA8)的定位和干扰素刺激基因(ISG)的表达。FEZ1通过控制HSPA8的核质穿梭,参与DNA依赖性蛋白激酶(DNA-PK)的积累,进而影响ISG的表达,从而在HSPA8/DNA-PK先天免疫通路中发挥调节作用[1]。此外,FEZ1还参与HIV-1病毒粒子的运输和干扰素刺激基因的表达,在HIV-1感染过程中发挥双重作用[5]。

FEZ1的表达异常与多种肿瘤的发生发展相关。FEZ1基因位于染色体8p22,该区域在多种肿瘤中频繁出现等位基因缺失。FEZ1基因的缺失或突变可能导致肿瘤细胞生长抑制和有丝分裂调控异常[6][9]。FEZ1的异常表达可能通过影响细胞周期的进展和细胞增殖,进而促进肿瘤的发生和发展。

综上所述,FEZ1是一种多功能性蛋白,在神经发育、免疫反应和肿瘤发生等方面发挥着重要作用。FEZ1的表达和功能异常与多种疾病的发生发展相关,包括神经发育障碍、精神分裂症、HIV-1感染和肿瘤等。深入研究FEZ1的功能和调控机制,有助于揭示相关疾病的发病机制,为疾病的诊断、治疗和预防提供新的思路和策略。

参考文献:
1. Malikov, Viacheslav, Meade, Nathan, Simons, Lacy M, Hultquist, Judd F, Naghavi, Mojgan H. . FEZ1 phosphorylation regulates HSPA8 localization and interferon-stimulated gene expression. In Cell reports, 38, 110396. doi:10.1016/j.celrep.2022.110396. https://pubmed.ncbi.nlm.nih.gov/35172151/
2. Alhesain, Maznah, Ronan, Hannah, LeBeau, Fiona E N, Clowry, Gavin J. 2023. Expression of the schizophrenia associated gene FEZ1 in the early developing fetal human forebrain. In Frontiers in neuroscience, 17, 1249973. doi:10.3389/fnins.2023.1249973. https://pubmed.ncbi.nlm.nih.gov/37746155/
3. Gunaseelan, Saravanan, Wang, Ziyin, Tong, Venetia Kok Jing, Lim, Kah-Leong, Chua, John Jia En. . Loss of FEZ1, a gene deleted in Jacobsen syndrome, causes locomotion defects and early mortality by impairing motor neuron development. In Human molecular genetics, 30, 5-20. doi:10.1093/hmg/ddaa281. https://pubmed.ncbi.nlm.nih.gov/33395696/
4. Qu, Yinghua, Lim, Jonathan Jun-Yong, An, Omer, Toh, Yi-Chin, Chua, John Jia En. 2023. FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migrations. In iScience, 26, 108497. doi:10.1016/j.isci.2023.108497. https://pubmed.ncbi.nlm.nih.gov/38213789/
5. Malikov, Viacheslav, Naghavi, Mojgan H. 2023. FEZ1 Plays Dual Roles in Early HIV-1 Infection by Independently Regulating Capsid Transport and Host Interferon-Stimulated Gene Expression. In Journal of virology, 97, e0049923. doi:10.1128/jvi.00499-23. https://pubmed.ncbi.nlm.nih.gov/37219433/
6. Ishii, H, Vecchione, A, Murakumo, Y, Baffa, R, Croce, C M. 2001. FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis. In Proceedings of the National Academy of Sciences of the United States of America, 98, 10374-9. doi:. https://pubmed.ncbi.nlm.nih.gov/11504921/
7. Chen, Xianjun, Ku, Li, Mei, Ruyi, Xiao, Lan, Feng, Yue. 2017. Novel schizophrenia risk factor pathways regulate FEZ1 to advance oligodendroglia development. In Translational psychiatry, 7, 1293. doi:10.1038/s41398-017-0028-z. https://pubmed.ncbi.nlm.nih.gov/29249816/
8. Vachev, T I, Stoyanova, V K, Ivanov, H Y, Minkov, I N, Popov, N T. 2015. Investigation of fasciculation and elongation protein ζ-1 (FEZ1) in peripheral blood reveals differences in gene expression in patients with schizophrenia. In Balkan journal of medical genetics : BJMG, 18, 31-8. doi:10.1515/bjmg-2015-0003. https://pubmed.ncbi.nlm.nih.gov/26929903/
9. Ishii, H, Baffa, R, Numata, S I, Alder, H, Croce, C M. . The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors. In Proceedings of the National Academy of Sciences of the United States of America, 96, 3928-33. doi:. https://pubmed.ncbi.nlm.nih.gov/10097140/