Ozawa Ritsuko, Hayashi Yukiko K, Ogawa Megumu, Kurokawa Rumi, Matsumoto Hiroshi, Noguchi Satoru, Nonaka Ikuya, Nishino Ichizo
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Am J Pathol. 2006 Mar;168(3):907-17. doi: 10.2353/ajpath.2006.050564.
Emery-Dreifuss muscular dystrophy is an inherited muscular disorder clinically characterized by slowly progressive weakness affecting humero-peroneal muscles, early joint contractures, and cardiomyopathy with conduction block. The X-linked recessive form is caused by mutation in the EMD gene encoding an integral protein of the inner nuclear membrane, emerin. In this study, mutant mice lacking emerin were produced by insertion of a neomycin resistance gene into exon 6 of the coding gene. Tissues taken from mutant mice lacked emerin. The mutant mice displayed a normal growth rate indistinguishable from their littermates and were fertile. No marked muscle weakness or joint abnormalities were observed; however, rotarod test revealed altered motor coordination. Electrocardiography showed mild prolongation of atrioventricular conduction time in emerin-lacking male mice older than 40 weeks of age. Electron microscopic analysis of skeletal and cardiac muscles from emerin-lacking mice revealed small vacuoles, which mostly bordered the myonuclei. Our results suggest that emerin deficiency causes minimal motor and cardiac dysfunctions in mice with a structural fragility of myonuclei.
埃默里-德赖富斯肌营养不良症是一种遗传性肌肉疾病，临床特征为缓慢进展的肌无力，累及肱腓肌，早期出现关节挛缩，以及伴有传导阻滞的心肌病。X连锁隐性型是由编码内核膜整合蛋白emerin的EMD基因突变引起的。在本研究中，通过将新霉素抗性基因插入编码基因的外显子6中，产生了缺乏emerin的突变小鼠。从突变小鼠身上获取的组织缺乏emerin。突变小鼠的生长速度正常，与同窝小鼠无差异，且具有生育能力。未观察到明显的肌肉无力或关节异常；然而，转棒试验显示运动协调性改变。心电图显示，年龄超过40周的缺乏emerin的雄性小鼠房室传导时间轻度延长。对缺乏emerin的小鼠的骨骼肌和心肌进行电子显微镜分析，发现有小空泡，这些小空泡大多与肌细胞核相邻。我们的结果表明，emerin缺乏在具有肌细胞核结构脆弱性的小鼠中引起最小程度的运动和心脏功能障碍。
