基因操作和烟碱型乙酰胆碱受体生物学的最新进展。
Recent advances in gene manipulation and nicotinic acetylcholine receptor biology.
机构信息
Institute for Behavioral Genetics, University of Colorado at Boulder, UCB 447, Boulder, CO 80309, United States.
出版信息
Biochem Pharmacol. 2011 Oct 15;82(8):808-19. doi: 10.1016/j.bcp.2011.06.014. Epub 2011 Jun 16.
Abstract
Pharmacological and immunological methods have been valuable for both identifying some native nicotinic acetylcholine receptor (nAChR) subtypes that exist in vivo and determining the neurobiological and behavioral role of certain nAChR subtypes. However, these approaches suffer from shortage of subtype specific ligands and reliable immunological reagents. Consequently, genetic approaches have been developed to complement earlier approaches to identify native nAChR subtypes and to assess the contribution of nAChRs to brain function and behavior. In this review we describe how assembly partners, knock-in mice and targeted lentiviral re-expression of genes have been utilized to improve our understanding of nAChR neurobiology. In addition, we summarize emerging genetic tools in nAChR research.
摘要
药理学和免疫学方法对于鉴定体内存在的某些天然烟碱型乙酰胆碱受体（nAChR）亚型以及确定某些 nAChR 亚型的神经生物学和行为作用都非常有价值。然而，这些方法存在亚型特异性配体和可靠免疫试剂的短缺。因此，已经开发了遗传方法来补充早期的方法，以鉴定天然 nAChR 亚型，并评估 nAChR 对大脑功能和行为的贡献。在这篇综述中，我们描述了如何利用组装伙伴、基因敲入小鼠和靶向慢病毒的重新表达来提高我们对 nAChR 神经生物学的理解。此外，我们还总结了 nAChR 研究中的新兴遗传工具。
相似文献
1
Recent advances in gene manipulation and nicotinic acetylcholine receptor biology.基因操作和烟碱型乙酰胆碱受体生物学的最新进展。
Biochem Pharmacol. 2011 Oct 15;82(8):808-19. doi: 10.1016/j.bcp.2011.06.014. Epub 2011 Jun 16.
2
Insights into the neurobiology of the nicotinic cholinergic system and nicotine addiction from mice expressing nicotinic receptors harboring gain-of-function mutations.从表达具有功能获得性突变的烟碱型乙酰胆碱能受体的小鼠中了解烟碱型乙酰胆碱能系统和尼古丁成瘾的神经生物学。
Pharmacol Rev. 2012 Oct;64(4):869-79. doi: 10.1124/pr.111.004671. Epub 2012 Aug 10.
3
Diversity of native nicotinic receptor subtypes in mammalian brain.哺乳动物大脑中天然烟碱受体亚型的多样性。
Neuropharmacology. 2015 Sep;96(Pt B):302-11. doi: 10.1016/j.neuropharm.2014.11.003. Epub 2014 Nov 25.
4
Physical and virtual screening methods for marine toxins and drug discovery targeting nicotinic acetylcholine receptors.用于海洋毒素和烟碱型乙酰胆碱受体为靶点的药物发现的物理和虚拟筛选方法。
Expert Opin Drug Discov. 2013 Oct;8(10):1203-23. doi: 10.1517/17460441.2013.822365. Epub 2013 Aug 6.
5
Structural differences determine the relative selectivity of nicotinic compounds for native alpha 4 beta 2*-, alpha 6 beta 2*-, alpha 3 beta 4*- and alpha 7-nicotine acetylcholine receptors.结构差异决定了烟碱化合物对天然 alpha 4 beta 2*-、alpha 6 beta 2*-、alpha 3 beta 4*-和 alpha 7-烟碱型乙酰胆碱受体的相对选择性。
Neuropharmacology. 2010 Jun;58(7):1054-66. doi: 10.1016/j.neuropharm.2010.01.013. Epub 2010 Jan 28.
6
Naturally-expressed nicotinic acetylcholine receptor subtypes.天然表达的烟碱型乙酰胆碱受体亚型。
Biochem Pharmacol. 2011 Oct 15;82(8):800-7. doi: 10.1016/j.bcp.2011.07.067. Epub 2011 Jul 20.
7
Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions.多种脑烟碱型胆碱能受体基因变异对尼古丁依赖的不同贡献：近期进展与新出现的开放性问题
Mol Psychiatry. 2009 Oct;14(10):912-45. doi: 10.1038/mp.2009.59. Epub 2009 Jun 30.
8
Analysis of rare variations reveals roles of amino acid residues in the N-terminal extracellular domain of nicotinic acetylcholine receptor (nAChR) alpha6 subunit in the functional expression of human alpha6*-nAChRs.罕见变异分析揭示了烟碱型乙酰胆碱受体（nAChR）α6亚基N端细胞外结构域中的氨基酸残基在人α6* - nAChRs功能表达中的作用。
Mol Brain. 2014 May 2;7:35. doi: 10.1186/1756-6606-7-35.
9
Spectral confocal imaging of fluorescently tagged nicotinic receptors in knock-in mice with chronic nicotine administration.对长期给予尼古丁的基因敲入小鼠中荧光标记的烟碱型受体进行光谱共聚焦成像。
J Vis Exp. 2012 Feb 10(60):3516. doi: 10.3791/3516.
10
The novel α7β2-nicotinic acetylcholine receptor subtype is expressed in mouse and human basal forebrain: biochemical and pharmacological characterization.新型α7β2-烟碱型乙酰胆碱受体亚型在小鼠和人类基底前脑表达：生化与药理学特性
Mol Pharmacol. 2014 Sep;86(3):306-17. doi: 10.1124/mol.114.093377. Epub 2014 Jul 7.
引用本文的文献
1
Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in the post-National Lung Screening Trial era.弥合临床差距：基因、表观遗传和转录组生物标志物在国家肺癌筛查试验后时代用于肺癌的早期检测。
BMC Med. 2013 Jul 19;11:168. doi: 10.1186/1741-7015-11-168.
2
Nicotine inhibits memory CTL programming.尼古丁抑制记忆 CTL 编程。
PLoS One. 2013 Jul 2;8(7):e68183. doi: 10.1371/journal.pone.0068183. Print 2013.
3
Genetic matters: thirty years of progress using mouse models in nicotinic research.遗传因素：利用尼古丁研究中的小鼠模型取得三十年的进展。
Biochem Pharmacol. 2013 Oct 15;86(8):1105-13. doi: 10.1016/j.bcp.2013.05.021. Epub 2013 Jun 6.
4
AAV-directed persistent expression of a gene encoding anti-nicotine antibody for smoking cessation.AAV 介导的编码抗尼古丁抗体的基因持续表达用于戒烟。
Sci Transl Med. 2012 Jun 27;4(140):140ra87. doi: 10.1126/scitranslmed.3003611.
5
Cotinine conundrum--a step forward but questions remain.可替宁难题——向前迈进了一步，但问题依然存在。
J Natl Cancer Inst. 2012 May 16;104(10):720-2. doi: 10.1093/jnci/djs211. Epub 2012 Apr 25.
6
Neurochemistry: Lighting up with azobenzenes.神经化学：偶氮苯点亮神经化学领域
Nat Chem. 2012 Jan 24;4(2):75-7. doi: 10.1038/nchem.1255.
本文引用的文献
1
The necessity of α4* nicotinic receptors in nicotine-driven behaviors: dissociation between reinforcing and motor effects of nicotine.α4* 烟碱型乙酰胆碱受体在尼古丁驱动行为中的必要性：尼古丁的强化作用和运动效应的分离。
Neuropsychopharmacology. 2011 Jun;36(7):1505-17. doi: 10.1038/npp.2011.35. Epub 2011 Mar 23.
2
Prefrontal nicotinic receptors control novel social interaction between mice.前额烟碱型乙酰胆碱受体控制小鼠之间新颖的社交互动。
FASEB J. 2011 Jul;25(7):2145-55. doi: 10.1096/fj.10-178558. Epub 2011 Mar 14.
3
Nicotine-mediated activation of dopaminergic neurons in distinct regions of the ventral tegmental area.尼古丁激活腹侧被盖区不同区域的多巴胺能神经元。
Neuropsychopharmacology. 2011 Apr;36(5):1021-32. doi: 10.1038/npp.2010.240. Epub 2011 Feb 2.
4
Habenular α5 nicotinic receptor subunit signalling controls nicotine intake.缰核 α5 型烟碱型乙酰胆碱受体亚基信号传导控制尼古丁摄入。
Nature. 2011 Mar 31;471(7340):597-601. doi: 10.1038/nature09797. Epub 2011 Jan 30.
5
Nicotinic acetylcholine receptors containing the α4 subunit are critical for the nicotine-induced reduction of acute voluntary ethanol consumption.含α4 亚基的烟碱型乙酰胆碱受体对于尼古丁诱导的急性自愿性乙醇消耗减少至关重要。
Channels (Austin). 2011 Mar-Apr;5(2):124-7. doi: 10.4161/chan.5.2.14409. Epub 2011 Mar 1.
6
Optogenetics.光遗传学。
Nat Methods. 2011 Jan;8(1):26-9. doi: 10.1038/nmeth.f.324. Epub 2010 Dec 20.
7
Activation of alpha4* nAChRs is necessary and sufficient for varenicline-induced reduction of alcohol consumption.α4*nAChRs 的激活对于伐伦克林减少酒精消耗是必要且充分的。
J Neurosci. 2010 Jul 28;30(30):10169-76. doi: 10.1523/JNEUROSCI.2601-10.2010.
8
Cholinergic modulation of locomotion and striatal dopamine release is mediated by alpha6alpha4* nicotinic acetylcholine receptors.乙酰胆碱能调制运动和纹状体多巴胺释放是由α6α4* 型烟碱型乙酰胆碱受体介导的。
J Neurosci. 2010 Jul 21;30(29):9877-89. doi: 10.1523/JNEUROSCI.2056-10.2010.
9
Genomewide association studies and assessment of the risk of disease.全基因组关联研究与疾病风险评估
N Engl J Med. 2010 Jul 8;363(2):166-76. doi: 10.1056/NEJMra0905980.
10
Altered activity-rest patterns in mice with a human autosomal-dominant nocturnal frontal lobe epilepsy mutation in the β2 nicotinic receptor.β2 型烟碱型乙酰胆碱受体的人类常染色体显性夜间额叶癫痫突变小鼠的活动-休息模式改变。
Mol Psychiatry. 2011 Oct;16(10):1048-61. doi: 10.1038/mp.2010.78. Epub 2010 Jul 6.
Zotero 插件