Kcnj6-flox 基因敲除小鼠

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产品名称

Kcnj6-flox 基因敲除小鼠

产品编号

S-CKO-03231

品系全称

C57BL/6JCya-Kcnj6em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-16522-Kcnj6-B6J-VA

品系状态

使用本品系发表的文献需注明: Kcnj6-flox 基因敲除小鼠 mice (Strain S-CKO-03231) 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
potassium inwardly-rectifying channel, subfamily J, member 6
基因别称
BIR1,GIRK2,KATP2,KCNJ7,Kir3.2,weaver,wv
染色体号
Chr 16 (Mouse)
转录本 ID
NCBI: NM_001025590 | Ensembl: ENSMUST00000165538
修饰方式
条件性基因敲除
靶向范围
Exon 2
敲除长度
~1.4 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:104781A spontaneous mutation exhibits small size, ataxia, hypotonia, high periweaning mortality, Purkinje cell defects, and male sterility. Homozygotes for a targeted null mutation exhibit increased susceptibility to spontaneous and drug-induced seizures.
Kcnj6,也称为GIRK2,是一种编码G蛋白偶联内向整流钾通道亚基的基因。GIRK通道在神经元网络中发挥着重要的调节作用,通过调节神经元兴奋性,影响神经元的电活动。Kcnj6基因位于人类染色体21上,其编码的GIRK2亚基与G蛋白偶联受体(GPCRs)相互作用,参与多种神经生物学过程,包括认知功能、奖赏机制和突触可塑性。

Kcnj6基因的变异与多种神经精神疾病相关。例如,研究发现Kcnj6基因的SNP(单核苷酸多态性)与奖赏相关的脑过程有关,可能影响注意力缺陷/多动症(ADHD)的风险[3]。此外,Kcnj6基因的剂量增加与唐氏综合征(DS)的行为和海马突触可塑性缺陷相关[1],表明Kcnj6基因在神经发育和认知功能中发挥重要作用。

Kcnj6基因的变异还与疼痛相关表型相关。研究发现Kcnj6基因的SNPs与疼痛相关表型有关,包括术后镇痛需求[6]和慢性疼痛强度[2]。这些研究提示Kcnj6基因可能影响疼痛信号传递和镇痛效果,为个性化疼痛治疗提供潜在靶点。

Kcnj6基因的变异还与酒精依赖相关。研究发现Kcnj6基因的SNP与成年酒精依赖相关,并可能影响早期生活压力对青少年饮酒的影响[4]。此外,研究发现酒精可以逆转Kcnj6基因变异对人类谷氨酸能神经元兴奋性的影响[5],提示Kcnj6基因可能在酒精依赖的病理机制中发挥作用。

综上所述,Kcnj6基因在神经生物学过程中发挥着重要作用,其变异与多种神经精神疾病、疼痛和酒精依赖相关。未来研究需要进一步探讨Kcnj6基因变异的生物学功能和临床应用价值,为相关疾病的诊断、治疗和预防提供新的思路和策略。

参考文献:
1. Kleschevnikov, Alexander M, Yu, Jessica, Kim, Jeesun, Yu, Y Eugene, Mobley, William C. 2017. Evidence that increased Kcnj6 gene dose is necessary for deficits in behavior and dentate gyrus synaptic plasticity in the Ts65Dn mouse model of Down syndrome. In Neurobiology of disease, 103, 1-10. doi:10.1016/j.nbd.2017.03.009. https://pubmed.ncbi.nlm.nih.gov/28342823/
2. Bruehl, Stephen, Denton, Jerod S, Lonergan, Daniel, Mishra, Puneet, Thornton-Wells, Tricia A. 2013. Associations between KCNJ6 (GIRK2) gene polymorphisms and pain-related phenotypes. In Pain, 154, 2853-2859. doi:10.1016/j.pain.2013.08.026. https://pubmed.ncbi.nlm.nih.gov/23994450/
3. Ziegler, Georg C, Röser, Christoph, Renner, Tobias, Reif, Andreas, Lesch, Klaus-Peter. 2019. KCNJ6 variants modulate reward-related brain processes and impact executive functions in attention-deficit/hyperactivity disorder. In American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 183, 247-257. doi:10.1002/ajmg.b.32734. https://pubmed.ncbi.nlm.nih.gov/31099984/
4. Clarke, Toni-Kim, Laucht, Manfred, Ridinger, Monika, Desrivieres, Sylvane, Schumann, Gunter. 2011. KCNJ6 is associated with adult alcohol dependence and involved in gene × early life stress interactions in adolescent alcohol drinking. In Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 36, 1142-8. doi:10.1038/npp.2010.247. https://pubmed.ncbi.nlm.nih.gov/21307845/
5. Popova, Dina, Gameiro-Ros, Isabel, Youssef, Mark M, Slesinger, Paul A, Hart, Ronald P. 2022. Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons. In Molecular psychiatry, 28, 746-758. doi:10.1038/s41380-022-01818-x. https://pubmed.ncbi.nlm.nih.gov/36207584/
6. Nishizawa, Daisuke, Nagashima, Makoto, Katoh, Ryoji, Hayashida, Masakazu, Ikeda, Kazutaka. 2009. Association between KCNJ6 (GIRK2) gene polymorphisms and postoperative analgesic requirements after major abdominal surgery. In PloS one, 4, e7060. doi:10.1371/journal.pone.0007060. https://pubmed.ncbi.nlm.nih.gov/19756153/