DIAPHRAGM DISPLAYS EARLY AND PROGRESSIVE FUNCTIONAL DEFICITS IN DYSFERLIN-DEFICIENT MICE
DIAPHRAGM DISPLAYS EARLY AND PROGRESSIVE FUNCTIONAL DEFICITS IN DYSFERLIN-DEFICIENT MICE
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DOI：
10.1002/mus.21645
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发表时间：
2010-07-01
期刊：
影响因子：
3.4
通讯作者：
Sweeney, H. Lee
中科院分区：
文献类型：
--
作者：
Barton, Elisabeth R.;Wang, Bing Jing;Sweeney, H. Lee
患有dysferlin缺乏症的小鼠系是肢带型肌营养不良症2B和Miyoshi肌病的公认动物模型，但病理学进展缓慢阻碍了对这种疾病的潜在疗法的快速筛选。我们的目标是确定缺乏dysferlin的骨骼肌的功能特征。力的产生和偏心性收缩损伤的敏感性的测量进行了孤立的肢体肌肉和膈肌从10和36周龄的A/J和年龄匹配的对照小鼠。肢体肌肉在10周和36周时具有正常的比力，而膈肌在比力和对离心收缩损伤的敏感性方面都有显著的缺陷。隔膜在离心收缩过程中的膜破裂主要发生在肌球蛋白重链2A表达纤维。Dysferlin含量在野生型肌肉之间没有显着变化，表明疾病严重程度和正常内源性蛋白水平之间没有相关性。这些研究表明，与肢体肌肉不同，A/J小鼠的横膈膜显示出早期功能缺陷，这可能会降低评估dysferlinopathies潜在疗法所需的年龄。肌肉神经42：22-29，2010
Mouse lines with dysferlin deficiency are accepted animal models for limb girdle muscular dystrophy 2B and Miyoshi myopathy, yet slow progression of pathology prevents rapid screening of potential therapies for this disease. Our goal was to define a functional signature for skeletal muscles that lack dysferlin. Force generation and susceptibility to eccentric contractile injury measurements were performed in isolated limb muscles and the diaphragm from 10- and 36-week-old A/J and age-matched control mice. Limb muscles had normal specific force at both 10 and 36 weeks, whereas the diaphragm had significant deficits in both specific force and susceptibility to eccentric contractile injury. Membrane ruptures in the diaphragm during eccentric contractions occurred predominantly in myosin heavy chain 2A-expressing fibers. Dysferlin content did not vary significantly between wildtype muscles, suggesting that there was no correlation between disease severity and normal endogenous levels of the protein. These studies show that, unlike limb muscles, the diaphragm from the A/J mouse displays early deficits in function that may lower the age needed for evaluating potential therapies for dysferlinopathies. Muscle Nerve 42: 22-29, 2010