Of Mice and Men: Advances in the Understanding of Neuromuscular Aspects of Myotonic Dystrophy.
Of Mice and Men: Advances in the Understanding of Neuromuscular Aspects of Myotonic Dystrophy.
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DOI：
10.3389/fneur.2018.00519
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发表时间：
2018
影响因子：
3.4
通讯作者：
Gomes-Pereira M
中科院分区：
文献类型：
--
作者：
Braz SO;Acquaire J;Gourdon G;Gomes-Pereira M
人们一直致力于在小鼠中建立强直性肌营养不良（DM）模型，以重现人类疾病并提供有用的工具来研究分子和细胞发病机制并测试有效的疗法。小鼠模型通过有毒 RNA 转录本的表达，有助于剖析 DM 突变对各种组织、细胞类型和多效性途径的多方面影响。不同组织中选择性剪接、转录、翻译、细胞内 RNA 定位、聚腺苷酸化、miRNA 代谢和疾病中间体磷酸化的变化已被描述。其中一些事件与小鼠骨骼肌和心脏的特定疾病症状直接相关，为个体疾病表型提供分子解释。然而，在中枢神经系统（CNS）中，情况更为复杂。我们仍然不知道所描述的分子异常如何转化为中枢神经系统功能障碍，也不知道纠正单个分子事件是否会带来显着的治疗益处。迄今为止描述的模型设计和表型的可变性需要进行彻底和批判性的分析。在这篇综述中，我们讨论了小鼠模型最近对理解疾病的神经肌肉方面、治疗发展的贡献，并对我们当前的局限性和尚未解答的紧迫问题进行了反思性评估。
Intensive effort has been directed toward the modeling of myotonic dystrophy (DM) in mice, in order to reproduce human disease and to provide useful tools to investigate molecular and cellular pathogenesis and test efficient therapies. Mouse models have contributed to dissect the multifaceted impact of the DM mutation in various tissues, cell types and in a pleiotropy of pathways, through the expression of toxic RNA transcripts. Changes in alternative splicing, transcription, translation, intracellular RNA localization, polyadenylation, miRNA metabolism and phosphorylation of disease intermediates have been described in different tissues. Some of these events have been directly associated with specific disease symptoms in the skeletal muscle and heart of mice, offering the molecular explanation for individual disease phenotypes. In the central nervous system (CNS), however, the situation is more complex. We still do not know how the molecular abnormalities described translate into CNS dysfunction, nor do we know if the correction of individual molecular events will provide significant therapeutic benefits. The variability in model design and phenotypes described so far requires a thorough and critical analysis. In this review we discuss the recent contributions of mouse models to the understanding of neuromuscular aspects of disease, therapy development, and we provide a reflective assessment of our current limitations and pressing questions that remain unanswered.
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影响因子：
4
作者：
Coonrod LA;Nakamori M;Wang W;Carrell S;Hilton CL;Bodner MJ;Siboni RB;Docter AG;Haley MM;Thornton CA;Berglund JA
通讯作者：
Berglund JA
影响因子：
3.5
作者：
Chamberlain, Christopher M.;Ranum, Laura P. W.
通讯作者：
Ranum, Laura P. W.
影响因子：
3.7
作者：
Cardani, Rosanna;Bugiardini, Enrico;Meola, Giovanni
通讯作者：
Meola, Giovanni
影响因子：
4.3
作者：
Bargiela A;Cerro-Herreros E;Fernandez-Costa JM;Vilchez JJ;Llamusi B;Artero R
通讯作者：
Artero R
影响因子：
11.1
作者：
Choi, Jongkyu;Personius, Kirkwood E.;Reddy, Sita
通讯作者：
Reddy, Sita