利用γ-氨基丁酸A型受体α6亚基转基因将基因表达导向小脑颗粒细胞。
Directing gene expression to cerebellar granule cells using gamma-aminobutyric acid type A receptor alpha6 subunit transgenes.
作者信息
Bahn S, Jones A, Wisden W
机构信息
Medical Research Council Laboratory of Molecular Biology, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom.
出版信息
Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9417-21. doi: 10.1073/pnas.94.17.9417.
Abstract
Expression of the gamma-aminobutyric acid type A receptor alpha6 subunit gene is restricted to differentiated granule cells of the cerebellum and cochlear nucleus. The mechanisms underlying this limited expression are unknown. Here we have characterized the expression of a series of alpha6-based transgenes in adult mouse brain. A DNA fragment containing a 1-kb portion upstream of the start site(s), together with exons 1-8, can direct high-level cerebellar granule cell-specific reporter gene expression. Thus powerful granule cell-specific determinants reside within the 5' half of the alpha6 subunit gene body. This intron-containing transgene appears to lack the cochlear nucleus regulatory elements. It therefore provides a cassette to deliver gene products solely to adult cerebellar granule cells.
摘要
γ-氨基丁酸A型受体α6亚基基因的表达仅限于小脑和耳蜗核的分化颗粒细胞。这种有限表达背后的机制尚不清楚。在这里，我们已经对成年小鼠大脑中一系列基于α6的转基因的表达进行了表征。一个包含起始位点上游1 kb部分以及外显子1 - 8的DNA片段，可以指导高水平的小脑颗粒细胞特异性报告基因表达。因此，强大的颗粒细胞特异性决定因素存在于α6亚基基因体的5'半部分内。这个含内含子的转基因似乎缺乏耳蜗核调节元件。因此，它提供了一个仅将基因产物递送至成年小脑颗粒细胞的盒式载体。
相似文献
1
Directing gene expression to cerebellar granule cells using gamma-aminobutyric acid type A receptor alpha6 subunit transgenes.利用γ-氨基丁酸A型受体α6亚基转基因将基因表达导向小脑颗粒细胞。
Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9417-21. doi: 10.1073/pnas.94.17.9417.
2
The intrinsic specification of gamma-aminobutyric acid type A receptor alpha6 subunit gene expression in cerebellar granule cells.小脑颗粒细胞中γ-氨基丁酸A型受体α6亚基基因表达的内在调控
Eur J Neurosci. 1999 Jun;11(6):2194-8. doi: 10.1046/j.1460-9568.1999.00662.x.
3
A minimal promoter for the GABA(A) receptor alpha6-subunit gene controls tissue specificity.γ-氨基丁酸A（GABA(A)）受体α6亚基基因的最小启动子控制组织特异性。
J Neurochem. 2000 May;74(5):1858-69. doi: 10.1046/j.1471-4159.2000.0741858.x.
4
Aβ40 modulates GABA(A) receptor α6 subunit expression and rat cerebellar granule neuron maturation through the ERK/mTOR pathway.Aβ40 通过 ERK/mTOR 通路调节 GABA(A) 受体 α6 亚基表达和大鼠小脑颗粒神经元成熟。
J Neurochem. 2014 Feb;128(3):350-62. doi: 10.1111/jnc.12471. Epub 2013 Oct 24.
5
Characterization of a cerebellar granule cell-specific gene encoding the gamma-aminobutyric acid type A receptor alpha 6 subunit.一种编码γ-氨基丁酸A型受体α6亚基的小脑颗粒细胞特异性基因的特性分析。
J Neurochem. 1996 Sep;67(3):907-16. doi: 10.1046/j.1471-4159.1996.67030907.x.
6
GABAA alpha6-containing receptors are selectively compromised in cerebellar granule cells of the ataxic mouse, stargazer.含有GABAA α6的受体在共济失调小鼠“凝视者”的小脑颗粒细胞中选择性受损。
J Biol Chem. 2007 Oct 5;282(40):29130-43. doi: 10.1074/jbc.M700111200. Epub 2007 Jul 23.
7
Transient increase in cerebellar transcriptional activity precedes the expression of GABA(A) receptor alpha6 subunit mRNA during postnatal maturation.在出生后成熟过程中，小脑转录活性的短暂增加先于GABA(A)受体α6亚基mRNA的表达。
Dev Neurosci. 1998;20(1):74-82. doi: 10.1159/000017301.
8
AMPA receptors serum-dependently mediate GABAA receptor alpha1 and alpha6 subunit down-regulation in cultured mouse cerebellar granule cells.AMPA 受体在血清依赖性条件下调节培养的小鼠小脑颗粒细胞 GABA A 受体 α1 和 α6 亚基的下调。
Neurochem Int. 2010 Apr;56(5):720-6. doi: 10.1016/j.neuint.2010.02.009. Epub 2010 Feb 16.
9
Differential effects of methylmercury on gamma-aminobutyric acid type A receptor currents in rat cerebellar granule and cerebral cortical neurons in culture.甲基汞对培养的大鼠小脑颗粒神经元和大脑皮质神经元中γ-氨基丁酸A型受体电流的不同影响。
J Pharmacol Exp Ther. 2008 Feb;324(2):517-28. doi: 10.1124/jpet.107.123976. Epub 2007 Oct 31.
10
Selective transgene expression in cerebellar Purkinje cells and granule cells using adeno-associated viruses together with specific promoters.利用腺相关病毒与特定启动子在小脑浦肯野细胞和颗粒细胞中进行选择性转基因表达。
Brain Res. 2015 Sep 16;1620:1-16. doi: 10.1016/j.brainres.2015.05.015. Epub 2015 May 16.
引用本文的文献
1
Impaired cerebellar plasticity hypersensitizes sensory reflexes in SCN2A-associated ASD.小脑可塑性受损使SCN2A相关自闭症谱系障碍中的感觉反射超敏。
Neuron. 2024 May 1;112(9):1444-1455.e5. doi: 10.1016/j.neuron.2024.01.029. Epub 2024 Feb 26.
2
Bmi1 overexpression in the cerebellar granule cell lineage of mice affects cell proliferation and survival without initiating medulloblastoma formation.在小鼠小脑颗粒细胞谱系中过表达 Bmi1 不会引发成神经管细胞瘤形成，但会影响细胞增殖和存活。
Dis Model Mech. 2013 Jan;6(1):49-63. doi: 10.1242/dmm.009506. Epub 2012 Oct 12.
3
GABAergic inhibition of histaminergic neurons regulates active waking but not the sleep-wake switch or propofol-induced loss of consciousness.GABA 能抑制组胺能神经元调节觉醒活动，但不调节睡眠-觉醒转换或异丙酚诱导的意识丧失。
J Neurosci. 2012 Sep 19;32(38):13062-75. doi: 10.1523/JNEUROSCI.2931-12.2012.
4
Distributed synergistic plasticity and cerebellar learning.分布式协同可塑性与小脑学习。
Nat Rev Neurosci. 2012 Sep;13(9):619-35. doi: 10.1038/nrn3312. Epub 2012 Aug 16.
5
Studying Cerebellar Circuits by Remote Control of Selected Neuronal Types with GABA(A) Receptors.通过 GABA(A) 受体远程控制选定神经元类型来研究小脑回路。
Front Mol Neurosci. 2009 Dec 11;2:29. doi: 10.3389/neuro.02.029.2009. eCollection 2009.
6
The treasury of the commons: making use of public gene expression resources to better characterize the molecular diversity of inhibitory interneurons in the cerebellar cortex.公有基因表达资源库：利用公共基因表达资源更好地描述小脑皮层抑制性中间神经元的分子多样性。
Cerebellum. 2009 Dec;8(4):477-89. doi: 10.1007/s12311-009-0124-6. Epub 2009 Jun 25.
7
Expression of NR2B in cerebellar granule cells specifically facilitates effect of motor training on motor learning.小脑颗粒细胞中NR2B的表达特别有助于运动训练对运动学习的影响。
PLoS One. 2008 Feb 27;3(2):e1684. doi: 10.1371/journal.pone.0001684.
8
Reversible suppression of glutamatergic neurotransmission of cerebellar granule cells in vivo by genetically manipulated expression of tetanus neurotoxin light chain.通过基因操纵破伤风神经毒素轻链的表达在体内可逆性抑制小脑颗粒细胞的谷氨酸能神经传递。
J Neurosci. 2003 Jul 30;23(17):6759-67. doi: 10.1523/JNEUROSCI.23-17-06759.2003.
9
Cre-mediated recombination in rhombic lip derivatives.菱形唇衍生物中的Cre介导的重组。
Genesis. 2002 Aug;33(4):160-9. doi: 10.1002/gene.10104.
10
Mouse cerebellar granule cell differentiation: electrical activity regulates the GABAA receptor alpha 6 subunit gene.小鼠小脑颗粒细胞分化：电活动调节GABAA受体α6亚基基因。
J Neurosci. 1998 Apr 15;18(8):2822-33. doi: 10.1523/JNEUROSCI.18-08-02822.1998.
本文引用的文献
1
Cerebellar circuits and synaptic mechanisms involved in classical eyeblink conditioning.经典眨眼条件反射中涉及的小脑回路和突触机制。
Trends Neurosci. 1997 Apr;20(4):177-81. doi: 10.1016/s0166-2236(96)10081-3.
2
The GABAA receptor alpha 6 subunit gene (Gabra6) is tightly linked to the alpha 1-gamma 2 subunit cluster on mouse chromosome 11.
Brain Res Mol Brain Res. 1997 Apr;45(1):133-7. doi: 10.1016/s0169-328x(96)00290-2.
3
Variegated gene expression in mice.小鼠中的斑驳基因表达。
Trends Genet. 1997 Apr;13(4):127-30. doi: 10.1016/s0168-9525(97)01097-4.
4
Attentional activation of the cerebellum independent of motor involvement.小脑的注意力激活与运动参与无关。
Science. 1997 Mar 28;275(5308):1940-3. doi: 10.1126/science.275.5308.1940.
5
Insensitivity to anaesthetic agents conferred by a class of GABA(A) receptor subunit.一类GABA(A)受体亚基赋予的对麻醉剂不敏感。
Nature. 1997 Feb 27;385(6619):820-3. doi: 10.1038/385820a0.
6
Genes involved in cerebellar cell specification and differentiation.参与小脑细胞特化与分化的基因。
Curr Opin Neurobiol. 1997 Feb;7(1):40-7. doi: 10.1016/s0959-4388(97)80118-3.
7
The cerebellum: a model system for studying GABAA receptor diversity.小脑：研究GABAA受体多样性的模型系统。
Neuropharmacology. 1996;35(9-10):1139-60. doi: 10.1016/s0028-3908(96)00076-7.
8
Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene inactivation inhibits delta subunit expression.配体门控离子通道亚基伙伴关系：GABAA受体α6亚基基因失活抑制δ亚基表达。
J Neurosci. 1997 Feb 15;17(4):1350-62. doi: 10.1523/JNEUROSCI.17-04-01350.1997.
9
Subregion- and cell type-restricted gene knockout in mouse brain.小鼠大脑中特定亚区域和细胞类型的基因敲除
Cell. 1996 Dec 27;87(7):1317-26. doi: 10.1016/s0092-8674(00)81826-7.
10
Control of memory formation through regulated expression of a CaMKII transgene.通过钙调蛋白激酶II转基因的调控表达来控制记忆形成。
Science. 1996 Dec 6;274(5293):1678-83. doi: 10.1126/science.274.5293.1678.
Zotero 插件