Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3
Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3
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DOI：
10.1016/s1567-133x(03)00064-4
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发表时间：
2003-08-01
影响因子：
1.2
通讯作者：
Swanson, MS
中科院分区：
文献类型：
--
作者：
Kanadia, RN;Urbinati, CR;Swanson, MS
强直性肌营养不良DM1和DM2的RNA介导的发病机制模型认为，受影响基因的突变转录产物将一系列双链RNA结合因子--肌盲蛋白MBNL1、MBNL2和MBNL3--隔离在细胞核中。这些蛋白质是果蝇肌肉盲蛋白的同系物，是肌肉和光感受器组织的终末分化所必需的，因此人类蛋白质的核隔离可能会损害它们在肌肉和眼睛的发育和维持中的正常功能。为了进一步检验这一模型，我们分析了小鼠MBNL1、Mbnl2和Mbnl3基因在胚胎发育过程中的表达模式，并将肌盲基因的表达与DMPK进行了比较，因为DM1的RNA致病模型需要突变的DMPK转录本和肌盲蛋白的协调合成。我们的研究表明，在肢体、神经系统和各种肌肉(包括横隔膜和舌头)的发育过程中，DMPK和肌肉盲基因的表达存在显著重叠。(C)2003 Elsevier Science B.V.保留所有权利。
The RNA-mediated pathogenesis model for the myotonic dystrophies DM1 and DM2 proposes that mutant transcripts from the affected genes sequester a family of double-stranded RNA-binding factors, the muscleblind proteins MBNL1, MBNL2 and MBNL3, in the nucleus. These proteins are homologues of the Drosophila muscleblind proteins that are required for the terminal differentiation of muscle and photoreceptor tissues, and thus nuclear sequestration of the human proteins might impair their normal function in muscle and eye development and maintenance. To examine this model further, we analyzed the expression pattern of the mouse Mbnl1, Mbnl2, and Mbnl3 genes during embryonic development and compared muscleblind gene expression to Dmpk since the RNA pathogenesis model for DM1 requires the coordinate synthesis of mutant Dmpk transcripts and muscleblind proteins. Our studies reveal a striking overlap between the expression of Dmpk and the muscleblind genes during development of the limbs, nervous system and various muscles, including the diaphragm and tongue. (C) 2003 Elsevier Science B.V. All rights reserved.