突变型LRRK2（R1441G）细菌人工染色体转基因小鼠重现了帕金森病的主要特征。
Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease.
作者信息
Li Yanping, Liu Wencheng, Oo Tinmarla F, Wang Lei, Tang Yi, Jackson-Lewis Vernice, Zhou Chun, Geghman Kindiya, Bogdanov Mikhail, Przedborski Serge, Beal M Flint, Burke Robert E, Li Chenjian
机构信息
Department of Neurology and Neurosciences, Weill Medical College of Cornell University, New York, New York, USA.
出版信息
Nat Neurosci. 2009 Jul;12(7):826-8. doi: 10.1038/nn.2349. Epub 2009 Jun 7.
Abstract
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease. We created a LRRK2 transgenic mouse model that recapitulates cardinal features of the disease: an age-dependent and levodopa-responsive slowness of movement associated with diminished dopamine release and axonal pathology of nigrostriatal dopaminergic projection. These mice provide a valid model of Parkinson's disease and are a resource for the investigation of pathogenesis and therapeutics.
摘要
富含亮氨酸重复激酶2（LRRK2）的突变是帕金森病最常见的遗传病因。我们创建了一种LRRK2转基因小鼠模型，该模型概括了该疾病的主要特征：与多巴胺释放减少和黑质纹状体多巴胺能投射的轴突病理相关的年龄依赖性和左旋多巴反应性运动迟缓。这些小鼠提供了一种有效的帕金森病模型，是研究发病机制和治疗方法的资源。
相似文献
1
Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease.突变型LRRK2（R1441G）细菌人工染色体转基因小鼠重现了帕金森病的主要特征。
Nat Neurosci. 2009 Jul;12(7):826-8. doi: 10.1038/nn.2349. Epub 2009 Jun 7.
2
LRRK2 BAC transgenic rats develop progressive, L-DOPA-responsive motor impairment, and deficits in dopamine circuit function.携带LRRK2细菌人工染色体的转基因大鼠出现进行性、对左旋多巴有反应的运动障碍以及多巴胺回路功能缺陷。
Hum Mol Genet. 2016 Mar 1;25(5):951-63. doi: 10.1093/hmg/ddv628. Epub 2016 Jan 6.
3
Selective expression of Parkinson's disease-related Leucine-rich repeat kinase 2 G2019S missense mutation in midbrain dopaminergic neurons impairs dopamine release and dopaminergic gene expression.帕金森病相关的富含亮氨酸重复激酶2 G2019S错义突变在中脑多巴胺能神经元中的选择性表达会损害多巴胺释放及多巴胺能基因表达。
Hum Mol Genet. 2015 Sep 15;24(18):5299-312. doi: 10.1093/hmg/ddv249. Epub 2015 Jun 29.
4
Mouse models for LRRK2 Parkinson's disease.LRRK2 帕金森病的小鼠模型。
Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S186-9. doi: 10.1016/S1353-8020(11)70058-X.
5
Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson's disease mutation G2019S.LRRK2 过表达增强了小鼠纹状体多巴胺传递和运动表现，而家族性帕金森病突变 G2019S 则消除了这种作用。
J Neurosci. 2010 Feb 3;30(5):1788-97. doi: 10.1523/JNEUROSCI.5604-09.2010.
6
Temporal expression of mutant LRRK2 in adult rats impairs dopamine reuptake.突变 LRRK2 在成年大鼠中的时间表达会损害多巴胺摄取。
Int J Biol Sci. 2011;7(6):753-61. doi: 10.7150/ijbs.7.753. Epub 2011 Jun 9.
7
Diapocynin prevents early Parkinson's disease symptoms in the leucine-rich repeat kinase 2 (LRRK2R¹⁴⁴¹G) transgenic mouse.滇罂粟宁可预防富含亮氨酸重复激酶 2（LRRK2R¹⁴⁴¹G）转基因小鼠的早期帕金森病症状。
Neurosci Lett. 2013 Aug 9;549:57-62. doi: 10.1016/j.neulet.2013.05.034. Epub 2013 May 28.
8
A rat model of progressive nigral neurodegeneration induced by the Parkinson's disease-associated G2019S mutation in LRRK2.LRRK2 相关帕金森病 G2019S 突变诱导的进行性黑质神经退行性变大鼠模型。
J Neurosci. 2011 Jan 19;31(3):907-12. doi: 10.1523/JNEUROSCI.5092-10.2011.
9
Non-motor and motor features in LRRK2 transgenic mice.LRRK2 转基因小鼠的非运动和运动特征。
PLoS One. 2013 Jul 30;8(7):e70249. doi: 10.1371/journal.pone.0070249. Print 2013.
10
Homozygous mutation of the LRRK2 ROC domain as a novel genetic model of parkinsonism.LRRK2 ROC 结构域纯合突变：一种新型帕金森病遗传学模型。
J Biomed Sci. 2022 Aug 14;29(1):60. doi: 10.1186/s12929-022-00844-9.
引用本文的文献
1
MicroRNAs and synaptic dysfunction in Parkinson's disease.帕金森病中的微小RNA与突触功能障碍
Mol Ther Nucleic Acids. 2025 Aug 12;36(3):102673. doi: 10.1016/j.omtn.2025.102673. eCollection 2025 Sep 9.
2
The Human LRRK2-R1441G Mutation Drives Age-Dependent Oxidative Stress and Mitochondrial Dysfunction in Dopaminergic Neurons.人类LRRK2-R1441G突变导致多巴胺能神经元中与年龄相关的氧化应激和线粒体功能障碍。
bioRxiv. 2025 Jun 17:2025.06.16.660029. doi: 10.1101/2025.06.16.660029.
3
Accumulation of LRRK2-associated phospho-Rab12 degenerative lysosomes in tauopathies.富含亮氨酸重复激酶2相关磷酸化Rab12的退行性溶酶体在tau蛋白病中的积累。
bioRxiv. 2025 Jun 9:2025.06.06.658328. doi: 10.1101/2025.06.06.658328.
4
Temporal progression of pathological features in an α-synuclein overexpression model of Parkinson's disease.帕金森病α-突触核蛋白过表达模型中病理特征的时间进程
Brain Struct Funct. 2025 Jun 9;230(6):91. doi: 10.1007/s00429-025-02959-9.
5
Environmental Factors Exacerbate Parkinsonian Phenotypes in an Asian-Specific Knock-In LRRK2 Risk Variant in Mice.环境因素加剧亚洲特异性敲入LRRK2风险变体小鼠的帕金森病表型。
Int J Mol Sci. 2025 Apr 10;26(8):3556. doi: 10.3390/ijms26083556.
6
Research models to study lewy body dementia.用于研究路易体痴呆的研究模型。
Mol Neurodegener. 2025 Apr 23;20(1):46. doi: 10.1186/s13024-025-00837-w.
7
An update on mammalian and non-mammalian animal models for biomarker development in neurodegenerative disorders.神经退行性疾病生物标志物开发的哺乳动物和非哺乳动物动物模型的最新进展。
Cell Mol Life Sci. 2025 Apr 7;82(1):147. doi: 10.1007/s00018-025-05668-y.
8
The homozygous LRRK2.p.N1437D point mutation mouse is a novel model of parkinsonism.纯合型LRRK2.p.N1437D点突变小鼠是帕金森病的一种新型模型。
NPJ Parkinsons Dis. 2025 Mar 28;11(1):61. doi: 10.1038/s41531-025-00905-4.
9
Scattering approach to diffusion quantifies axonal damage in brain injury.扩散的散射方法可量化脑损伤中的轴突损伤。
ArXiv. 2025 Jan 30:arXiv:2501.18167v1.
10
Genetic mutations in kinases: a comprehensive review on marketed inhibitors and unexplored targets in Parkinson's disease.激酶中的基因突变：帕金森病上市抑制剂及未探索靶点的综合综述
Neurol Sci. 2025 Apr;46(4):1509-1524. doi: 10.1007/s10072-024-07970-2. Epub 2025 Jan 6.
本文引用的文献
1
Haplotypes and gene expression implicate the MAPT region for Parkinson disease: the GenePD Study.单倍型和基因表达表明帕金森病与微管相关蛋白tau（MAPT）区域有关：基因帕金森病研究。
Neurology. 2008 Jul 1;71(1):28-34. doi: 10.1212/01.wnl.0000304051.01650.23. Epub 2008 May 28.
2
Tau-mediated neurodegeneration in Alzheimer's disease and related disorders.阿尔茨海默病及相关疾病中tau蛋白介导的神经退行性变。
Nat Rev Neurosci. 2007 Sep;8(9):663-72. doi: 10.1038/nrn2194.
3
A comparative analysis of leucine-rich repeat kinase 2 (Lrrk2) expression in mouse brain and Lewy body disease.富含亮氨酸重复激酶2（Lrrk2）在小鼠脑和路易体病中的表达比较分析
Neuroscience. 2007 Jul 29;147(4):1047-58. doi: 10.1016/j.neuroscience.2007.05.027. Epub 2007 Jul 3.
4
Increased frequency of the LRRK2 G2019S mutation in an elderly Ashkenazi Jewish population is not associated with dementia.老年阿什肯纳兹犹太人群中LRRK2 G2019S突变频率增加与痴呆症无关。
Neurosci Lett. 2006 Jul 10;402(1-2):92-6. doi: 10.1016/j.neulet.2006.03.044. Epub 2006 Apr 24.
5
In vivo imaging of axonal degeneration and regeneration in the injured spinal cord.损伤脊髓中轴突退变与再生的体内成像
Nat Med. 2005 May;11(5):572-7. doi: 10.1038/nm1229. Epub 2005 Apr 10.
6
A common LRRK2 mutation in idiopathic Parkinson's disease.特发性帕金森病中一种常见的LRRK2突变。
Lancet. 2005;365(9457):415-6. doi: 10.1016/S0140-6736(05)17830-1.
7
A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease.一种与常染色体显性帕金森病相关的常见LRRK2基因突变。
Lancet. 2005;365(9457):412-5. doi: 10.1016/S0140-6736(05)17829-5.
8
Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology.LRRK2基因的突变会导致具有多形性病理特征的常染色体显性帕金森病。
Neuron. 2004 Nov 18;44(4):601-7. doi: 10.1016/j.neuron.2004.11.005.
9
Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease.导致与PARK8相关帕金森病的含突变基因的克隆。
Neuron. 2004 Nov 18;44(4):595-600. doi: 10.1016/j.neuron.2004.10.023.
10
Parkinson's disease: mechanisms and models.帕金森病：机制与模型
Neuron. 2003 Sep 11;39(6):889-909. doi: 10.1016/s0896-6273(03)00568-3.
Zotero 插件