Emerin-lacking mice show minimal motor and cardiac dysfunctions with nuclear-associated vacuoles
Emerin-lacking mice show minimal motor and cardiac dysfunctions with nuclear-associated vacuoles
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DOI：
10.2353/ajpath.2006.050564
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发表时间：
2006-03-01
影响因子：
6
通讯作者：
Nishino, I
中科院分区：
文献类型：
--
作者：
Ozawa, R;Hayashi, YK;Nishino, I
Emery-Dreifuss肌营养不良症是一种遗传性肌肉疾病，临床特征为缓慢进行性无力累及腓总肌，早期关节痉挛，以及伴有传导阻滞的心肌病。这种X连锁的隐性形式是由编码内核膜完整蛋白质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到编码基因的外显子6中，产生了缺乏Emerin的突变小鼠。从突变小鼠身上提取的组织缺乏Emerin。突变的小鼠表现出正常的生长速度，与它们的小鼠难以区分，并且是可生育的。没有观察到明显的肌肉无力或关节异常；然而，旋转棒测试显示运动协调性改变。心电图显示，40周龄以上缺乏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的电子显微镜分析显示，小空泡主要与肌核接壤。我们的结果表明，Emerin缺乏会导致肌核结构脆弱的小鼠轻微的运动和心脏功能障碍。
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.