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利用斑马鱼建立自闭症谱系障碍模型:斑马鱼与其哺乳动物对应物中自闭症谱系障碍风险基因的比较。

Using Zebrafish to Model Autism Spectrum Disorder: A Comparison of ASD Risk Genes Between Zebrafish and Their Mammalian Counterparts.

作者信息

Rea Victoria, Van Raay Terence J

机构信息

Dept of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada.

出版信息

Front Mol Neurosci. 2020 Nov 11;13:575575. doi: 10.3389/fnmol.2020.575575. eCollection 2020.

Abstract

Autism spectrum disorders (ASDs) are a highly variable and complex set of neurological disorders that alter neurodevelopment and cognitive function, which usually presents with social and learning impairments accompanied with other comorbid symptoms like hypersensitivity or hyposensitivity, or repetitive behaviors. Autism can be caused by genetic and/or environmental factors and unraveling the etiology of ASD has proven challenging, especially given that different genetic mutations can cause both similar and different phenotypes that all fall within the autism spectrum. Furthermore, the list of ASD risk genes is ever increasing making it difficult to synthesize a common theme. The use of rodent models to enhance ASD research is invaluable and is beginning to unravel the underlying molecular mechanisms of this disease. Recently, zebrafish have been recognized as a useful model of neurodevelopmental disorders with regards to genetics, pharmacology and behavior and one of the main foundations supporting autism research (SFARI) recently identified 12 ASD risk genes with validated zebrafish mutant models. Here, we describe what is known about those 12 ASD risk genes in human, mice and zebrafish to better facilitate this research. We also describe several non-genetic models including pharmacological and gnotobiotic models that are used in zebrafish to study ASD.

摘要

自闭症谱系障碍(ASD)是一组高度可变且复杂的神经障碍,会改变神经发育和认知功能,通常表现为社交和学习障碍,并伴有其他共病症状,如过敏或感觉迟钝,或重复行为。自闭症可能由遗传和/或环境因素引起,事实证明,揭示ASD的病因具有挑战性,特别是考虑到不同的基因突变可能导致所有都属于自闭症谱系的相似和不同表型。此外,ASD风险基因的清单不断增加,难以归纳出一个共同的主题。使用啮齿动物模型来加强ASD研究非常宝贵,并且开始揭示这种疾病的潜在分子机制。最近,斑马鱼在遗传学、药理学和行为方面已被公认为是神经发育障碍的有用模型,支持自闭症研究的主要基础之一(SFARI)最近通过经过验证的斑马鱼突变模型鉴定出12个ASD风险基因。在此,我们描述关于人类、小鼠和斑马鱼中这12个ASD风险基因的已知信息,以更好地推动这项研究。我们还描述了几种非遗传模型,包括用于斑马鱼研究ASD的药理学和无菌动物模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af36/7686559/222f0b03a4d9/fnmol-13-575575-g001.jpg

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