Hakim Chady H, Mijailovic Alex, Lessa Thais B, Coates Joan R, Shin Carmen, Rutkove Seward B, Duan Dongsheng
Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri, Columbia, MO, United States of America.
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
PLoS One. 2017 Mar 24;12(3):e0173557. doi: 10.1371/journal.pone.0173557. eCollection 2017.
Dystrophin-deficient dogs are by far the best available large animal models for Duchenne muscular dystrophy (DMD), the most common lethal childhood muscle degenerative disease. The use of the canine DMD model in basic disease mechanism research and translational studies will be greatly enhanced with the development of reliable outcome measures. Electrical impedance myography (EIM) is a non-invasive painless procedure that provides quantitative data relating to muscle composition and histology. EIM has been extensively used in neuromuscular disease research in both human patients and rodent models. Recent studies suggest that EIM may represent a highly reliable and convenient outcome measure in DMD patients and the mdx mouse model of DMD. To determine whether EIM can be used as a biomarker of disease severity in the canine model, we performed the assay in fourteen young (6.6-m-old; 6 normal and 8 affected) and ten mature (16.9-m-old; 4 normal and 6 affected) dogs of mixed background breeds. EIM was well tolerated with good inter-rater reliability. Affected dogs showed higher resistance, lower reactance and phase. The difference became more straightforward in mature dogs. Importantly, we observed a statistically significant correlation between the EIM data and muscle fibrosis. Our results suggest that EIM is a valuable objective measurement in the canine DMD model.
肌营养不良蛋白缺陷犬是目前用于杜兴氏肌肉营养不良症（DMD，最常见的致命性儿童肌肉退行性疾病）的最佳大型动物模型。随着可靠结果测量方法的发展，犬类DMD模型在基础疾病机制研究和转化研究中的应用将得到极大加强。电阻抗肌电图（EIM）是一种非侵入性无痛检查，可提供与肌肉组成和组织学相关的定量数据。EIM已广泛应用于人类患者和啮齿动物模型的神经肌肉疾病研究。最近的研究表明，EIM可能是DMD患者和DMD的mdx小鼠模型中一种高度可靠且便捷的结果测量方法。为了确定EIM是否可作为犬类模型中疾病严重程度的生物标志物，我们对14只年轻（约6.6月龄；6只正常，8只患病）和10只成熟（约16.9月龄；4只正常，6只患病）的混合背景品种犬进行了该检测。EIM耐受性良好，评分者间可靠性高。患病犬表现出更高的电阻、更低的电抗和相位。这种差异在成熟犬中变得更加明显。重要的是，我们观察到EIM数据与肌肉纤维化之间存在统计学上的显著相关性。我们的结果表明，EIM在犬类DMD模型中是一种有价值的客观测量方法。
