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斑马鱼如何推动基于遗传的听力和平衡研究的未来。

How Zebrafish Can Drive the Future of Genetic-based Hearing and Balance Research.

机构信息

Department of Otolaryngology-Head & Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.

Section On Sensory Cell Development and Function, National Institutes On Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, USA.

出版信息

J Assoc Res Otolaryngol. 2021 Jun;22(3):215-235. doi: 10.1007/s10162-021-00798-z. Epub 2021 Apr 28.

Abstract

Over the last several decades, studies in humans and animal models have successfully identified numerous molecules required for hearing and balance. Many of these studies relied on unbiased forward genetic screens based on behavior or morphology to identify these molecules. Alongside forward genetic screens, reverse genetics has further driven the exploration of candidate molecules. This review provides an overview of the genetic studies that have established zebrafish as a genetic model for hearing and balance research. Further, we discuss how the unique advantages of zebrafish can be leveraged in future genetic studies. We explore strategies to design novel forward genetic screens based on morphological alterations using transgenic lines or behavioral changes following mechanical or acoustic damage. We also outline how recent advances in CRISPR-Cas9 can be applied to perform reverse genetic screens to validate large sequencing datasets. Overall, this review describes how future genetic studies in zebrafish can continue to advance our understanding of inherited and acquired hearing and balance disorders.

摘要

在过去的几十年中,人类和动物模型的研究已经成功地确定了许多听觉和平衡所需的分子。这些研究中的许多都依赖于基于行为或形态的无偏正向遗传筛选来识别这些分子。除了正向遗传筛选,反向遗传学进一步推动了候选分子的探索。本综述提供了一个概述,介绍了将斑马鱼确立为听觉和平衡研究遗传模型的遗传研究。此外,我们还讨论了如何利用斑马鱼的独特优势来进行未来的遗传研究。我们探讨了如何使用转基因系或机械或声学损伤后行为变化,基于形态改变设计新的基于正向遗传筛选的策略。我们还概述了如何将 CRISPR-Cas9 的最新进展应用于进行反向遗传筛选,以验证大型测序数据集。总的来说,本综述描述了未来的斑马鱼遗传研究如何继续推进我们对遗传性和获得性听力和平衡障碍的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46c9/8110678/60294c72cbe1/10162_2021_798_Fig1_HTML.jpg

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