Fischer Matthias, Raabe Thomas
Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany.
Institute of Medical Radiation and Cell Research, Biozentrum, University of Würzburg, Würzburg, Germany.
Front Behav Neurosci. 2018 May 23;12:106. doi: 10.3389/fnbeh.2018.00106. eCollection 2018.
Loss of function mutations in the gene cause Coffin-Lowry syndrome (CLS), which is associated with multiple symptoms including severe mental disabilities. Despite the characterization of ribosomal S6 kinase 2 (RSK2) as a protein kinase acting as a downstream effector of the well characterized ERK MAP-kinase signaling pathway, it turns out to be a challenging task to link RSK2 to specific neuronal processes dysregulated in case of mutation. Animal models such as mouse and combine advanced genetic manipulation tools with imaging techniques, high-resolution connectome analysis and a variety of behavioral assays, thereby allowing for an in-depth analysis for gene functions in the nervous system. Although modeling mental disability in animal systems has limitations because of the complexity of phenotypes, the influence of genetic variation and species-specific characteristics at the neural circuit and behavioral level, some common aspects of RSK2 function in the nervous system have emerged, which will be presented. Only with this knowledge our understanding of the pathophysiology of CLS can be improved, which might open the door for development of potential intervention strategies.
该基因功能丧失突变会导致科芬-洛里综合征（CLS），其与多种症状相关，包括严重智力残疾。尽管核糖体S6激酶2（RSK2）被鉴定为一种蛋白激酶，作为已充分表征的ERK丝裂原活化蛋白激酶信号通路的下游效应器，但将RSK2与突变时失调的特定神经元过程联系起来却是一项具有挑战性的任务。小鼠等动物模型将先进的基因操作工具与成像技术、高分辨率连接组分析及各种行为测定相结合，从而能够深入分析基因在神经系统中的功能。尽管由于表型的复杂性、遗传变异的影响以及神经回路和行为水平上的物种特异性特征，在动物系统中模拟智力残疾存在局限性，但RSK2在神经系统中的一些共同功能方面已显现出来，本文将予以介绍。只有掌握这些知识，我们对CLS病理生理学的理解才能得到改善，这可能为潜在干预策略的开发打开大门。
