Grin2a-flox 基因敲除小鼠

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产品名称

Grin2a-flox 基因敲除小鼠

产品编号

S-CKO-02755

品系全称

C57BL/6JCya-Grin2aem1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-14811-Grin2a-B6J-VA

品系状态

使用本品系发表的文献需注明: Grin2a-flox 基因敲除小鼠 mice (Strain S-CKO-02755) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
每周秒杀
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, NMDA2A (epsilon 1)
基因别称
GluN2A,GluRepsilon1,NMDAR2A,NR2A
染色体号
Chr 16 (Mouse)
转录本 ID
NCBI: NM_008170 | Ensembl: ENSMUST00000199708
修饰方式
条件性基因敲除
靶向范围
Exon 4
敲除长度
~1.8 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:95820Homozygotes for targeted null mutations exhibit jumpiness, mildly impaired long-term potentiation and spatial learning, increased locomotor activity and metabolism of dopamine and serotonin, and loss of analgesic tolerance after repeated morphine doses.
Grin2a基因编码NR2A(GluN2A)亚基,是N-甲基-D-天冬氨酸(NMDA)受体的重要组成部分。NMDA受体是离子型谷氨酸受体的一种,在突触传递和突触可塑性中发挥着关键作用。Grin2a基因的突变与多种神经系统疾病相关,包括精神分裂症、癫痫和言语障碍[1][2][3][4][5][6][7][8][9][10]。

Grin2a基因的突变可以导致NMDA受体功能异常,从而影响神经元的兴奋性和突触可塑性。Grin2a基因的罕见杂合子功能缺失(LoF)突变会导致精神分裂症的风险增加。在Grin2a突变小鼠模型中,观察到大脑区域特异性的神经元和胶质细胞基因表达变化,以及多巴胺信号传导的失调[4]。这些发现支持了精神分裂症的双重假设,即“低谷氨酸”和“高多巴胺”假说。

Grin2a基因的突变也与癫痫相关,尤其是儿童局灶性癫痫。Grin2a基因的突变可以导致NMDA受体功能异常,从而影响神经元的兴奋性和突触可塑性。Grin2a基因的突变还与言语障碍相关,如言语失用症和言语困难症。Grin2a基因的突变可以导致NMDA受体功能异常,从而影响言语运动功能。

Grin2a基因的研究对于理解神经系统的发育和功能具有重要意义。Grin2a基因的突变与多种神经系统疾病相关,包括精神分裂症、癫痫和言语障碍。Grin2a基因的研究有助于深入理解神经系统的发育和功能,以及神经系统疾病的发病机制。

参考文献:
1. Harrison, Paul J, Bannerman, David M. 2023. GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia. In Molecular psychiatry, 28, 3568-3572. doi:10.1038/s41380-023-02265-y. https://pubmed.ncbi.nlm.nih.gov/37736757/
2. Symonds, Joseph D, Zuberi, Sameer M, Johnson, Michael R. . Advances in epilepsy gene discovery and implications for epilepsy diagnosis and treatment. In Current opinion in neurology, 30, 193-199. doi:10.1097/WCO.0000000000000433. https://pubmed.ncbi.nlm.nih.gov/28212175/
3. Trubetskoy, Vassily, Pardiñas, Antonio F, Qi, Ting, Walters, James T R, O'Donovan, Michael C. 2022. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. In Nature, 604, 502-508. doi:10.1038/s41586-022-04434-5. https://pubmed.ncbi.nlm.nih.gov/35396580/
4. Farsi, Zohreh, Nicolella, Ally, Simmons, Sean K, Levin, Joshua Z, Sheng, Morgan. 2023. Brain-region-specific changes in neurons and glia and dysregulation of dopamine signaling in Grin2a mutant mice. In Neuron, 111, 3378-3396.e9. doi:10.1016/j.neuron.2023.08.004. https://pubmed.ncbi.nlm.nih.gov/37657442/
5. Turner, Samantha J, Mayes, Angela K, Verhoeven, Andrea, Morgan, Angela T, Scheffer, Ingrid E. 2015. GRIN2A: an aptly named gene for speech dysfunction. In Neurology, 84, 586-93. doi:10.1212/WNL.0000000000001228. https://pubmed.ncbi.nlm.nih.gov/25596506/
6. Davoudian, Pasha A, Shao, Ling-Xiao, Kwan, Alex C. 2023. Shared and Distinct Brain Regions Targeted for Immediate Early Gene Expression by Ketamine and Psilocybin. In ACS chemical neuroscience, 14, 468-480. doi:10.1021/acschemneuro.2c00637. https://pubmed.ncbi.nlm.nih.gov/36630309/
7. Luo, Xian, Yang, Kaiming, Jiang, Meiling, Lai, Liangxue, Zou, Qingjian. 2023. Generation of a homozygous GRIN2A gene knockout human embryonic stem cell line using CRISPR/Cas9 system. In Stem cell research, 69, 103121. doi:10.1016/j.scr.2023.103121. https://pubmed.ncbi.nlm.nih.gov/37182381/
8. Korinek, M, Candelas Serra, M, Abdel Rahman, Fes, Balik, A, Smejkalova, T. 2024. Disease-Associated Variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA Receptor Structure, Function, and Pathophysiology. In Physiological research, 73, S413-S434. doi:. https://pubmed.ncbi.nlm.nih.gov/38836461/
9. Samanta, Debopam. 2022. GRIN2A-related epilepsy and speech disorders: A comprehensive overview with a focus on the role of precision therapeutics. In Epilepsy research, 189, 107065. doi:10.1016/j.eplepsyres.2022.107065. https://pubmed.ncbi.nlm.nih.gov/36516565/
10. Bobbili, Dheeraj R, Lal, Dennis, May, Patrick, Lerche, Holger, Neubauer, Bernd A. 2018. Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy. In European journal of human genetics : EJHG, 26, 258-264. doi:10.1038/s41431-017-0034-x. https://pubmed.ncbi.nlm.nih.gov/29358611/