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秀丽隐杆线虫的穴居行为:研究神经肌肉疾病的新方法。

The burrowing behavior of the nematode Caenorhabditis elegans: a new assay for the study of neuromuscular disorders.

机构信息

Department of Neuroscience, Center for Brain, Behavior & Evolution; Waggoner Center for Alcohol and Addiction Research, Center for Learning and Memory, The University of Texas at Austin, Austin, TX, 78712, USA.

出版信息

Genes Brain Behav. 2015 Apr;14(4):357-68. doi: 10.1111/gbb.12217.

Abstract

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.

摘要

秀丽隐杆线虫是研究与人类神经肌肉功能和疾病相关的关键肌肉基因的有力模式生物。然而,秀丽隐杆线虫的行为稳健性阻碍了其在某些神经肌肉疾病研究中的应用,因为许多人类疾病的线虫模型在爬行时仅表现出细微的表型。相比之下,在其自然栖息地中,秀丽隐杆线虫可能会花费大量时间在土壤基质中挖掘。我们开发了一种挖掘 assay,通过将蠕虫放入密度逐渐增加的琼脂填充移液管中来挑战运动输出。我们发现挖掘涉及与基质特性相关的独特运动学和转向策略,与爬行不同。我们表明,通过缺乏功能性肌营养不良蛋白 DYS-1 类似物的突变体模仿杜氏肌营养不良症,其爬行正常,但在挖掘方面受到严重损害。在 dys-1 突变体中,挖掘会加速和加剧肌肉退化,而野生型则没有这种损伤。为了测试神经肌肉完整性是否可以在 dys-1 突变体中遗传补偿,我们进行了遗传筛选,并在 dys-1 突变体背景中分离出几个具有高效挖掘能力的抑制突变体。进一步研究秀丽隐杆线虫的挖掘行为将增强对影响神经肌肉完整性的疾病的研究,并为了解这种线虫和其他线虫的自然行为提供线索。

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