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利用斑马鱼遗传学理解心肌肌节组装

Understanding cardiac sarcomere assembly with zebrafish genetics.

作者信息

Yang Jingchun, Shih Yu-Huan, Xu Xiaolei

机构信息

Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota; Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota.

出版信息

Anat Rec (Hoboken). 2014 Sep;297(9):1681-93. doi: 10.1002/ar.22975.

Abstract

Mutations in sarcomere genes have been found in many inheritable human diseases, including hypertrophic cardiomyopathy. Elucidating the molecular mechanisms of sarcomere assembly shall facilitate understanding of the pathogenesis of sarcomere-based cardiac disease. Recently, biochemical and genomic studies have identified many new genes encoding proteins that localize to the sarcomere. However, their precise functions in sarcomere assembly and sarcomere-based cardiac disease are unknown. Here, we review zebrafish as an emerging vertebrate model for these studies. We summarize the techniques offered by this animal model to manipulate genes of interest, annotate gene expression, and describe the resulting phenotypes. We survey the sarcomere genes that have been investigated in zebrafish and discuss the potential of applying this in vivo model for larger-scale genetic studies.

摘要

在许多可遗传性人类疾病中都发现了肌节基因的突变,包括肥厚型心肌病。阐明肌节组装的分子机制将有助于理解基于肌节的心脏疾病的发病机制。最近,生物化学和基因组学研究已经鉴定出许多编码定位于肌节的蛋白质的新基因。然而,它们在肌节组装和基于肌节的心脏疾病中的精确功能尚不清楚。在此,我们综述了斑马鱼作为用于这些研究的新兴脊椎动物模型。我们总结了这种动物模型提供的用于操纵感兴趣基因、注释基因表达并描述由此产生的表型的技术。我们调查了在斑马鱼中已被研究的肌节基因,并讨论了将这种体内模型应用于大规模遗传研究的潜力。

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