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神经退行性疾病的转基因斑马鱼模型。

Transgenic zebrafish models of neurodegenerative diseases.

机构信息

Pittsburgh Institute for Neurodegenerative Diseases, School of Medicine, University of Pittsburgh, 7015 Biomedical Sciences Tower 3, 3501 Fifth Avenue, Pittsburgh, PA, 15260, USA.

出版信息

Brain Struct Funct. 2010 Mar;214(2-3):285-302. doi: 10.1007/s00429-009-0237-1. Epub 2010 Feb 17.

Abstract

Since the introduction of the zebrafish as a model for the study of vertebrate developmental biology, an extensive array of techniques for its experimental manipulation and analysis has been developed. Recently it has become apparent that these powerful methodologies might be deployed in order to elucidate the pathogenesis of human neurodegenerative diseases and to identify candidate therapeutic approaches. In this article, we consider evidence that the zebrafish central nervous system provides an appropriate setting in which to model human neurological disease and we review techniques and resources available for generating transgenic models. We then examine recent publications showing that appropriate phenotypes can be provoked in the zebrafish through transgenic manipulations analogous to genetic abnormalities known to cause human tauopathies, polyglutamine diseases or motor neuron degenerations. These studies show proof of concept that findings in zebrafish models can be applicable to the pathogenic mechanisms underlying human diseases. Consequently, the prospects for providing novel insights into neurodegenerative diseases by exploiting transgenic zebrafish models and discovery-driven approaches seem favorable.

摘要

自从斑马鱼被引入作为研究脊椎动物发育生物学的模型以来,已经开发出了大量用于其实验操作和分析的技术。最近,人们已经意识到,这些强大的方法学可以被用来阐明人类神经退行性疾病的发病机制,并确定候选治疗方法。在本文中,我们考虑了斑马鱼中枢神经系统为人类神经疾病建模提供合适环境的证据,并回顾了用于生成转基因模型的技术和资源。然后,我们研究了最近的一些出版物,这些出版物表明,通过类似于已知导致人类 tau 病、多聚谷氨酰胺疾病或运动神经元退行性变的遗传异常的转基因操作,可以在斑马鱼中引发适当的表型。这些研究证明了通过利用转基因斑马鱼模型和以发现为导向的方法,可以将斑马鱼模型中的发现应用于人类疾病的发病机制。因此,通过利用转基因斑马鱼模型和以发现为导向的方法,为神经退行性疾病提供新的见解的前景似乎是有利的。

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