Transgenic rodent models of Parkinson's disease.
Transgenic rodent models of Parkinson's disease.
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帕金森病的转基因啮齿动物模型。
DOI：
10.1007/978-3-211-78205-7_15
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Hoffer,BJ
中科院分区：
文献类型：
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作者：
Harvey,BK;Wang,Y;Hoffer,BJ
在帕金森病(PD)的研究中，经典的动物模型使用了多巴胺能神经毒素，如6-羟基多巴胺(6OHDA)和1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)。最近，人类遗传连锁研究已经在家族性帕金森病中发现了几个基因。已经建立了研究PD相关基因(如α-突触核蛋白、DJ-1、LRRK2、Parkin、UCH-L1、PINK1)功能的转基因模型。最近的证据表明，线粒体功能障碍可能在帕金森病的发病中起重要作用。操纵线粒体呼吸基因(例如线粒体转录因子A或TFAM)也会在小鼠中引起PD表型。转基因小鼠(MitoPark)是在多巴胺能神经元中选择性敲除TFAM的转基因小鼠。MitoPark小鼠的黑质多巴胺神经元表现出呼吸链功能障碍，伴随着神经元内包涵体的发展和最终的细胞死亡。在成年早期，MitoPark小鼠表现出伴随这些细胞变化的缓慢进展的运动功能丧失。MitoPark小鼠能够进一步研究DA神经元中线粒体功能障碍的作用，这是帕金森病发生发展的重要机制。转基因技术使人们对许多神经疾病的神经退化机制有了新的见解。本文就近年来帕金森病转基因模型的研究进展作一综述。
In the case of Parkinson’s disease (PD), classical animal models have utilized dopaminergic neurotoxins such as 6-hydroxydopamine (6OHDA) and 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP). More recently, human genetic linkage studies have identified several genes in familial forms of PD. Transgenic models have been made that explore the function of PD-linked genes (e.g. a-synuclein, DJ-1, LRRK2, Parkin, UCH-L1, PINK1). Recent evidence suggests mitochondrial dysfunction may play a major role in PD. Manipulation of mitochondrial respiratory genes (e.g. mitochondrial transcription factor A or TFAM) also elicits a PD phenotype in mice. Transgenic mice (MitoPark) were developed that have TFAM selectively knocked out in dopaminergic neurons. The nigral dopamine neurons of MitoPark mice show respiratory chain dysfunction, accompanied by the development of intraneuronal inclusions and eventual cell death. In early adulthood, the MitoPark mice show a slowly progressing loss of motor function that accompanies these cellular changes. The MitoPark mouse enables further study of the role of mitochondrial dysfunction in DA neurons as an important mechanism in the development of PD. Transgenic technology has allowed new insights into mechanisms of neurodegeneration for a number of neurological disorders. This paper will summarize recent studies on several transgenic models of PD.