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
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/