Singh Jaskaran, Patten Shunmoogum A
INRS - Centre Armand Frappier Santé Biotechnologie, Laval, QC, Canada.
Departement de Neurosciences, Université de Montréal, Montréal, QC, Canada.
Front Mol Neurosci. 2022 Dec 13;15:1054573. doi: 10.3389/fnmol.2022.1054573. eCollection 2022.
Neuromuscular diseases are a diverse group of conditions that affect the motor system and present some overlapping as well as distinct clinical manifestations. Although individually rare, the combined prevalence of NMDs is similar to Parkinson's. Over the past decade, new genetic mutations have been discovered through whole exome/genome sequencing, but the pathogenesis of most NMDs remains largely unexplored. Little information on the molecular mechanism governing the progression and development of NMDs accounts for the continual failure of therapies in clinical trials. Different aspects of the diseases are typically investigated using different models from cells to animals. Zebrafish emerges as an excellent model for studying genetics and pathogenesis and for developing therapeutic interventions for most NMDs. In this review, we describe the generation of different zebrafish genetic models mimicking NMDs and how they are used for drug discovery and therapy development.
神经肌肉疾病是一组影响运动系统的多种病症,具有一些重叠以及独特的临床表现。尽管每种神经肌肉疾病单独来看较为罕见,但它们的综合患病率与帕金森病相似。在过去十年中,通过全外显子组/基因组测序发现了新的基因突变,但大多数神经肌肉疾病的发病机制在很大程度上仍未得到探索。关于神经肌肉疾病进展和发展的分子机制的信息很少,这导致临床试验中的治疗持续失败。通常使用从细胞到动物的不同模型来研究疾病的不同方面。斑马鱼已成为研究遗传学和发病机制以及为大多数神经肌肉疾病开发治疗干预措施的优秀模型。在这篇综述中,我们描述了模拟神经肌肉疾病的不同斑马鱼遗传模型的构建,以及它们如何用于药物发现和治疗开发。