Haploinsuffciency for Znf9 in Znf9+/- mice is associated with multiorgan abnormalities resembling myotonic dystrophy
Haploinsuffciency for Znf9 in Znf9+/- mice is associated with multiorgan abnormalities resembling myotonic dystrophy
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DOI：
10.1016/j.jmb.2007.01.088
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发表时间：
2007-04-20
影响因子：
5.6
通讯作者：
Li, Yi-Ping
中科院分区：
文献类型：
--
作者：
Chen, Wei;Wang, Yucheng;Li, Yi-Ping
强直性肌营养不良2型是由ZNF9基因第一内含子(CCTG)/(CCUG)(N)重复扩增引起的。强直性肌营养不良的发病机制尚不清楚，ZNF9在2型强直性肌营养不良发病机制中的作用也不完全清楚。我们对表达显著降低的Znf9(+/-)小鼠进行了研究，发现它们的表型反映了强直性肌营养不良的许多特征，包括肌肉组织学形态，以及肌强直放电和心脏传导异常，分别由肌电图学和心电图分析显示。Znf9在心肌和骨骼肌中高表达，其中骨骼肌氯离子通道1(CLc1)起重要作用。在Znf9(+/-)小鼠中，CLc1的表达显著降低。转基因小鼠可上调其基因表达，挽救强直性肌营养不良表型。我们的结果表明，锌锌单倍体不足与强直性肌营养不良表型有关。(C)2007爱思唯尔有限公司。保留所有权利。
Myotonic dystrophy type 2 is caused by a (CCTG)/(CCUG)(n) repeat expansion in the first intron of the ZNF9 gene. The pathomechanism for the myotonic dystrophies is not well understood and the role of ZNF9 in myotonic dystrophy type 2 pathogenesis has not been fully clarified. We characterized Znf9(+/-) mice, in which the expression of Znf9 was significantly decreased, and found that their phenotype reflects many of the features of myotonic dystrophy, including muscle histological morphology, and myotonic discharges and heart conduction abnormalities, shown by electromyography and electrocardiogram analysis, respectively. Znf9 is normally highly expressed in heart and skeletal muscle, where skeletal muscle chloride channel 1 (Clc1) plays an important role. Clc1 expression was dramatically decreased in Znf9(+/-) mice. Znf9 transgenic mice raised Znf9 and Clcl expression and rescued the myotonic dystrophy phenotype in Znf9(+/-) mice. Our results suggest that the Znf9 haploinsufficiency contributes to the myotonic dystrophy phenotype in Znf9(+/-) mice. (c) 2007 Elsevier Ltd. All rights reserved.