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首页> 外文期刊>Genes, brain, and behavior >The burrowing behavior of the nematode Caenorhabditis elegans: a newassay for the study of neuromuscular disorders
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The burrowing behavior of the nematode Caenorhabditis elegans: a newassay for the study of neuromuscular disorders

机译:线虫秀丽隐杆线虫的穴居行为:研究神经肌肉疾病的新方法

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摘要

The nematode Caenorhabditis elegans has been a powerful model system for the study of key muscle genes relevant to human neuromuscular function and disorders. The behavioral robustness of C. elegans, however, has hindered its use in the study of certain neuromuscular disorders because many worm models of human disease show only subtle phenotypes while crawling. By contrast, in their natural habitat, C. elegans likely spends much of the time burrowing through the soil matrix. We developed a burrowing assay to challenge motor output by placing worms in agar-filled pipettes of increasing densities. We find that burrowing involves distinct kinematics and turning strategies from crawling that vary with the properties of the substrate. We show that mutants mimicking Duchenne muscular dystrophy by lacking a functional ortholog of the dystrophin protein, DYS-1, crawl normally but are severely impaired in burrowing. Muscular degeneration in the dys-1 mutant is hastened and exacerbated by burrowing, while wild type shows no such damage. To test whether neuromuscular integrity might be compensated genetically in the dys-1 mutant, we performed a genetic screen and isolated several suppressor mutants with proficient burrowing in a dys-1 mutant background. Further study of burrowing in C. elegans will enhance the study of diseases affecting neuromuscular integrity, and will provide insights into the natural behavior of this and other nematodes.
机译:线虫秀丽隐杆线虫已成为研究与人类神经肌肉功能和疾病有关的关键肌肉基因的强大模型系统。然而,秀丽隐杆线虫的行为稳健性阻碍了它在某些神经肌肉疾病研究中的使用,因为许多人类疾病蠕虫模型在爬行时仅表现出细微的表型。相比之下,秀丽隐杆线虫可能会在其自然栖息地中花费大量时间在土壤基质中挖洞。我们开发了一种穴位分析法,通过将蠕虫放入密度不断增加的琼脂填充的移液管中来挑战运动能力。我们发现挖洞涉及到不同的运动学和转向策略,这些策略和爬行策略随基材的性质而变化。我们显示突变体通过缺乏肌营养不良蛋白蛋白DYS-1的功能性直系同源物来模仿杜氏肌营养不良症,正常爬行,但在洞穴中严重受损。穴居使dys-1突变体的肌肉变性加速并加剧,而野生型则没有这种损害。为了测试在dys-1突变体中神经肌肉的完整性是否可以通过遗传方式得到补偿,我们进行了遗传筛选,并分离出了几个在dys-1突变体背景下具有熟练挖洞的抑制突变体。对秀丽隐杆线虫的穴位的进一步研究将加强对影响神经肌肉完整性的疾病的研究,并将提供对该线虫和其他线虫自然行为的见解。

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