Gria2-KO 基因敲除小鼠

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产品名称

Gria2-KO 基因敲除小鼠

产品编号

S-KO-02333

品系全称

C57BL/6JCya-Gria2em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-14800-Gria2-B6J-VA

品系状态

使用本品系发表的文献需注明: Gria2-KO 基因敲除小鼠 mice (Strain S-KO-02333) 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
glutamate receptor, ionotropic, AMPA2 (alpha 2)
基因别称
GluA2,GluR-B,Glur-2,Glur2,gluR-K2
染色体号
Chr 3 (Mouse)
转录本 ID
NCBI: NM_013540 | Ensembl: ENSMUST00000075316
修饰方式
全身性基因敲除
靶向范围
Exon 4
敲除长度
~0.2 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:95809Homozygotes for targeted null mutations exhibit epilepsy, deficient dendritic architecture, altered exploratory behavior, impaired motor and learning performance, and increased mortality.
Gria2,也称为GluA2,是人类编码AMPA受体(AMPARs)GluA2亚单位的基因。AMPA受体是谷氨酸能突触中主要的兴奋性离子通道,在神经信号传递、突触可塑性和神经发育中发挥关键作用。GluA2亚单位在AMPARs中具有特殊的重要性,因为它在Q607位点经过转录后编辑后,可以使异源多聚体AMPARs对Ca2+不渗透,从而影响电流与跨膜电压之间的关系。

Gria2基因的突变与多种神经发育障碍相关,包括智力障碍(ID)、自闭症谱系障碍(ASD)、Rett综合征样特征、癫痫或发育性癫痫性脑病(DEE)等。这些突变通常导致AMPARs功能受损,从而影响神经信号传递和突触可塑性。此外,Gria2基因的表达异常也与一些神经系统疾病有关,例如,Gria2基因的表达在胶质母细胞瘤(GBM)中显著上调,可以作为GBM患者生存预测的标志物。

在分子机制方面,Gria2基因的表达受到多种因素的调控。例如,miR-181a可以直接结合Gria2 mRNA的3'-UTR,下调Gria2的表达。此外,ADAR2 RNA编辑酶可以特异性地编辑Gria2基因的Q607位点,影响GluA2亚单位的功能和AMPARs的性质。

除了在神经系统中的作用外,Gria2基因的表达也与其他一些生物学过程相关。例如,Gria2基因的表达在软组织肿瘤中具有诊断价值,特别是在孤立性纤维瘤(SFT)中,Gria2基因的表达水平较高。此外,Gria2基因的表达也与血管平滑肌细胞的增殖和迁移相关,可能参与了动脉粥样硬化和血管再狭窄等血管疾病的发生发展。

综上所述,Gria2基因在神经系统中具有重要作用,其表达异常与多种神经发育障碍和神经系统疾病相关。Gria2基因的表达受到多种因素的调控,包括miR-181a和ADAR2 RNA编辑酶等。此外,Gria2基因的表达与其他一些生物学过程相关,例如软组织肿瘤和血管疾病。深入研究Gria2基因的功能和调控机制,有助于理解神经系统的发育和功能,为神经发育障碍和神经系统疾病的治疗提供新的思路和策略[1,2,3,4,5,6,7,8,9,10]。

参考文献:
1. Lebedeva, Maria, Kubištová, Aneta, Spišská, Veronika, Balík, Aleš, Bendová, Zdeňka. 2023. The disruption of circadian rhythmicity of gene expression in the hippocampus and associated structures in Gria2R/R mice; a comparison with C57BL/6J and Adar2-/- mice strains. In Brain research, 1826, 148739. doi:10.1016/j.brainres.2023.148739. https://pubmed.ncbi.nlm.nih.gov/38157956/
2. Salpietro, Vincenzo, Dixon, Christine L, Guo, Hui, Kullmann, Dimitri M, Houlden, Henry. 2019. AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders. In Nature communications, 10, 3094. doi:10.1038/s41467-019-10910-w. https://pubmed.ncbi.nlm.nih.gov/31300657/
3. Vivero, Marina, Doyle, Leona A, Fletcher, Christopher D M, Mertens, Fredrik, Hornick, Jason L. 2014. GRIA2 is a novel diagnostic marker for solitary fibrous tumour identified through gene expression profiling. In Histopathology, 65, 71-80. doi:10.1111/his.12377. https://pubmed.ncbi.nlm.nih.gov/24456377/
4. Zhang, Kai, Wang, Qingzhong, Jing, Xuxiu, Yu, Shunying, Zhao, Min. 2016. miR-181a is a negative regulator of GRIA2 in methamphetamine-use disorder. In Scientific reports, 6, 35691. doi:10.1038/srep35691. https://pubmed.ncbi.nlm.nih.gov/27767084/
5. Zhou, Bingbo, Zhang, Chuan, Zheng, Lei, Gu, Weiyue, Hui, Ling. 2021. Case Report: A Novel De Novo Missense Mutation of the GRIA2 Gene in a Chinese Case of Neurodevelopmental Disorder With Language Impairment. In Frontiers in genetics, 12, 794766. doi:10.3389/fgene.2021.794766. https://pubmed.ncbi.nlm.nih.gov/34899870/
6. Hajji, Khadija, Sedmík, Jiří, Cherian, Anna, Keegan, Liam P, O'Connell, Mary A. 2022. ADAR2 enzymes: efficient site-specific RNA editors with gene therapy aspirations. In RNA (New York, N.Y.), 28, 1281-1297. doi:10.1261/rna.079266.122. https://pubmed.ncbi.nlm.nih.gov/35863867/
7. Pan, Yuhualei, Zhang, Jian-Hua, Zhao, Lianhe, Wang, Huan, Zhu, Yan-Bing. 2020. A robust two-gene signature for glioblastoma survival prediction. In Journal of cellular biochemistry, 121, 3593-3605. doi:10.1002/jcb.29653. https://pubmed.ncbi.nlm.nih.gov/31960992/
8. Fang, Xingqiang, Yang, Songjian, Chen, Meixi, Peng, Peng, Zhao, Yongju. 2023. Association analysis of polymorphisms at GLRB, GRIA2, and GASK1B genes with reproductive traits in Dazu Black Goats. In Animal biotechnology, 34, 4721-4729. doi:10.1080/10495398.2023.2187406. https://pubmed.ncbi.nlm.nih.gov/36927330/
9. Huang, B L, Luo, H, Li, C Y, Wang, Y, Rong, S W. . [A case of neurodevelopmental disorder with refractory epilepsy caused by GRIA2 gene variant]. In Zhonghua er ke za zhi = Chinese journal of pediatrics, 60, 1209-1211. doi:10.3760/cma.j.cn112140-20220521-00470. https://pubmed.ncbi.nlm.nih.gov/36319160/
10. Zhou, Mi, Qi, Lixing, Gu, Yongquan. 2021. GRIA2/ENPP3 Regulates the Proliferation and Migration of Vascular Smooth Muscle Cells in the Restenosis Process Post-PTA in Lower Extremity Arteries. In Frontiers in physiology, 12, 712400. doi:10.3389/fphys.2021.712400. https://pubmed.ncbi.nlm.nih.gov/34504438/