Grina-flox 基因敲除小鼠

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产品名称

Grina-flox 基因敲除小鼠

产品编号

S-CKO-12919

品系全称

C57BL/6JCya-Grinaem1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-66168-Grina-B6J-VA

品系状态

使用本品系发表的文献需注明: Grina-flox 基因敲除小鼠 mice (Strain S-CKO-12919) 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
glutamate receptor, ionotropic, N-methyl D-aspartate-associated protein 1 (glutamate binding)
基因别称
1110025J15Rik,Lag,Tmbim3
染色体号
Chr 15 (Mouse)
转录本 ID
NCBI: NM_023168 | Ensembl: ENSMUST00000023225
修饰方式
条件性基因敲除
靶向范围
Exon 2~7
敲除长度
~4.0 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:1913418Mice homozygous for a null allele exhibit no significant alterations in behavior, histopathology or clinical chemistry.
基因GRINA,全称为Glutamate Receptor Ionotropic NMDA-Associated Protein 1,属于Lifeguard家族,参与钙离子稳态调控,对于细胞生存和神经递质释放等关键过程至关重要[1]。GRINA主要与内质网、高尔基体、内体和细胞表面的膜相关联,但其核内存在尚未得到解释[1]。研究发现,GRINA的细胞质N端半部分包含一个潜在的DNA结合序列,以及裂解靶点和可能的PY核定位序列,这使其能够在适当条件下从蛋白质的其他部分释放并进入细胞核,参与基因的转录、选择性剪接和mRNA输出,这些基因可能涉及脂质和甾醇合成、核糖体生物发生或细胞周期进程[1]。此外,GRINA还与多种疾病相关,包括精神分裂症、乳糜泻、高血脂症、骨关节炎、结直肠癌、胃癌和阿尔茨海默病等[1-10]。

研究发现,GRINA基因定位于人类染色体8q24区域,与良性家族性新生儿惊厥(BFNC)基因相距较远[2]。GRINA在细胞死亡调控中也发挥重要作用,其通过内质网应激反应中的PERK信号通路被上调,与TMBIM6/BI-1协同调控内质网钙离子稳态和细胞凋亡[3]。此外,GRINA的表达与高血脂症的风险相关,其DNA甲基化水平的升高会增加患高血脂症的风险[4]。在骨关节炎的研究中,GRINA被确定为骨关节炎风险的独立靶点,其表达在骨关节炎髋关节和非骨关节炎髋关节软骨之间表现出差异[5]。

在肿瘤研究中,GRINA的表达水平在结直肠癌和胃癌组织中显著升高,且与患者的预后不良相关[6,7]。GRINA的过表达可以显著增加结直肠癌和胃癌细胞的增殖、迁移和侵袭能力[6,7]。此外,GRINA的表达受miR-296-3p的负调控,miR-296-3p的表达水平与GRINA的表达呈负相关[6,7]。在阿尔茨海默病的研究中,GRINA的表达在脑缺血再灌注损伤后受到EPO的调节,GRINA的缺失会导致脑梗死体积增加,而EPO治疗可以上调GRINA的表达,减少脑梗死体积[8]。在抑郁症的研究中,GRINA的表达在抑郁症患者的额叶皮质中显著上调,这可能与抑郁症的病理机制相关[9]。

综上所述,GRINA在细胞钙离子稳态调控、细胞死亡、脂质代谢、骨关节炎、肿瘤和神经退行性疾病中发挥重要作用。GRINA的表达和功能调控可能成为治疗相关疾病的新靶点。

参考文献:
1. Jiménez-González, Víctor, Ogalla-García, Elena, García-Quintanilla, Meritxell, García-Quintanilla, Albert. 2019. Deciphering GRINA/Lifeguard1: Nuclear Location, Ca2+ Homeostasis and Vesicle Transport. In International journal of molecular sciences, 20, . doi:10.3390/ijms20164005. https://pubmed.ncbi.nlm.nih.gov/31426446/
2. Lewis, T B, Wood, S, Michaelis, E K, DuPont, B R, Leach, R J. . Localization of a gene for a glutamate binding subunit of a NMDA receptor (GRINA) to 8q24. In Genomics, 32, 131-3. doi:. https://pubmed.ncbi.nlm.nih.gov/8786101/
3. Rojas-Rivera, D, Armisén, R, Colombo, A, Stutzin, A, Hetz, C. 2012. TMBIM3/GRINA is a novel unfolded protein response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis. In Cell death and differentiation, 19, 1013-26. doi:10.1038/cdd.2011.189. https://pubmed.ncbi.nlm.nih.gov/22240901/
4. Liu, Shuai, Li, Yang, Wei, Xian, Fu, Zhen-Yan, Ma, Yi-Tong. 2022. Genetic analysis of DNA methylation in dyslipidemia: a case-control study. In PeerJ, 10, e14590. doi:10.7717/peerj.14590. https://pubmed.ncbi.nlm.nih.gov/36570009/
5. Rice, Sarah J, Tselepi, Maria, Sorial, Antony K, Reynard, Louise N, Loughlin, John. 2019. Prioritization of PLEC and GRINA as Osteoarthritis Risk Genes Through the Identification and Characterization of Novel Methylation Quantitative Trait Loci. In Arthritis & rheumatology (Hoboken, N.J.), 71, 1285-1296. doi:10.1002/art.40849. https://pubmed.ncbi.nlm.nih.gov/30730609/
6. Yan, Zaihua, Li, Peidong, Xue, Yuan, Zhou, Tong, Zhang, Guangjun. 2021. Glutamate receptor, ionotropic, N‑methyl D‑aspartate‑associated protein 1 promotes colorectal cancer cell proliferation and metastasis, and is negatively regulated by miR‑296‑3p. In Molecular medicine reports, 24, . doi:10.3892/mmr.2021.12339. https://pubmed.ncbi.nlm.nih.gov/34368871/
7. Ma, Huan, Zhang, Xianyu, Li, Na, Tian, Guiying, Li, Shuguang. 2020. Glutamate receptor, ionotropic, N-methyl D-aspartate-associated protein 1, a potential target of miR-296, facilitates proliferation and migration of rectal cancer cells. In Bioscience, biotechnology, and biochemistry, 84, 2077-2084. doi:10.1080/09168451.2020.1792267. https://pubmed.ncbi.nlm.nih.gov/32657216/
8. Habib, Pardes, Stamm, Ann-Sophie, Zeyen, Thomas, Schulz, Jörg B, Reich, Arno. 2019. EPO regulates neuroprotective Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) family members GRINA and FAIM2 after cerebral ischemia-reperfusion injury. In Experimental neurology, 320, 112978. doi:10.1016/j.expneurol.2019.112978. https://pubmed.ncbi.nlm.nih.gov/31211943/
9. Goswami, Dharmendra B, Jernigan, Courtney S, Chandran, Agata, Stockmeier, Craig A, Karolewicz, Beata. 2012. Gene expression analysis of novel genes in the prefrontal cortex of major depressive disorder subjects. In Progress in neuro-psychopharmacology & biological psychiatry, 43, 126-33. doi:10.1016/j.pnpbp.2012.12.010. https://pubmed.ncbi.nlm.nih.gov/23261523/