Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
MRC/ARUK Centre for Musculoskeletal Ageing Research, Royal Derby Hospital, University of Nottingham & National Institute for Health Research Nottingham Biomedical Research Centre, Derby, UK.
Dis Model Mech. 2018 Dec 4;11(12):dmm036137. doi: 10.1242/dmm.036137.
Muscle strength is a key clinical parameter used to monitor the progression of human muscular dystrophies, including Duchenne and Becker muscular dystrophies. Although is an established genetic model for studying the mechanisms and treatments of muscular dystrophies, analogous strength-based measurements in this disease model are lacking. Here, we describe the first demonstration of the direct measurement of muscular strength in dystrophin-deficient mutants using a micropillar-based force measurement system called NemaFlex We show that mutants, but not mutants, are significantly weaker than their wild-type counterparts in early adulthood, cannot thrash in liquid at wild-type rates, display mitochondrial network fragmentation in the body wall muscles, and have an abnormally high baseline mitochondrial respiration. Furthermore, treatment with prednisone, the standard treatment for muscular dystrophy in humans, and melatonin both improve muscular strength, thrashing rate and mitochondrial network integrity in , and prednisone treatment also returns baseline respiration to normal levels Thus, our results demonstrate that the strain is more clinically relevant than for muscular dystrophy studies in This finding, in combination with the novel NemaFlex platform, can be used as an efficient workflow for identifying candidate compounds that can improve strength in the muscular dystrophy model. Our study also lays the foundation for further probing of the mechanism of muscle function loss in dystrophin-deficient , leading to knowledge translatable to human muscular dystrophy.This article has an associated First Person interview with the first author of the paper.
肌肉力量是监测人类肌肉疾病（包括杜氏肌营养不良症和贝克肌营养不良症）进展的关键临床参数。虽然 是研究肌肉疾病机制和治疗方法的既定遗传模型，但在这种疾病模型中缺乏类似的基于力量的测量。在这里，我们首次展示了使用称为 NemaFlex 的基于微柱的力测量系统直接测量肌肉力量的能力，该系统可用于研究肌肉疾病。我们发现，与野生型相比， 突变体在成年早期明显较弱，不能以野生型的速度在液体中猛烈搅动，显示出体壁肌肉中线粒体网络的碎片化，并且具有异常高的基线线粒体呼吸。此外，用泼尼松（人类肌肉疾病的标准治疗方法）和褪黑素治疗均可改善 肌肉力量、猛烈搅动率和线粒体网络完整性，泼尼松治疗还可使基线呼吸恢复正常水平。因此，我们的研究结果表明，与 相比， 更适合用于研究肌肉疾病。这一发现，结合新型 NemaFlex 平台，可用于鉴定可改善 肌肉营养不良模型中力量的候选化合物的有效工作流程。我们的研究还为进一步探究肌营养不良症中肌肉功能丧失的机制奠定了基础，为可转化为人类肌肉疾病的知识奠定了基础。本文有该论文第一作者的相关第一人称采访。
