Melancia Francesca, Trezza Viviana
Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Rome, Italy.
Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Rome, Italy.
Behav Brain Res. 2018 Sep 17;350:149-163. doi: 10.1016/j.bbr.2018.04.042. Epub 2018 Apr 25.
Fragile X syndrome is the most common form of inherited mental retardation and the most frequent monogenic cause of syndromic autism spectrum disorders. The syndrome is caused by the loss of the Fragile X Mental Retardation Protein (FMRP), a key RNA-binding protein involved in synaptic plasticity and neuronal morphology. Patients show intellectual disability, social deficits, repetitive behaviors and impairments in social communication. The aim of this review is to outline the importance of behavioral phenotyping of animal models of FXS from a developmental perspective, by showing how the behavioral characteristics of FXS at the clinical level can be translated into effective, developmentally-specific and clinically meaningful behavioral readouts in the laboratory setting. After introducing the behavioral features, diagnostic criteria and off-label pharmacotherapy of FXS, we outline how FXS-relevant behavioral features can be modelled in laboratory animals in the course of development: we review the progress to date, discuss how behavioral phenotyping in animal models of FXS is essential to identify potential treatments, and discuss caveats and future directions in this research field.
脆性X综合征是遗传性智力障碍最常见的形式，也是综合征性自闭症谱系障碍最常见的单基因病因。该综合征是由脆性X智力障碍蛋白（FMRP）缺失引起的，FMRP是一种参与突触可塑性和神经元形态的关键RNA结合蛋白。患者表现出智力残疾、社交缺陷、重复行为以及社交沟通障碍。本综述的目的是从发育的角度概述脆性X综合征动物模型行为表型分析的重要性，展示临床水平上脆性X综合征的行为特征如何转化为实验室环境中有效、发育特异性且具有临床意义的行为读数。在介绍了脆性X综合征的行为特征、诊断标准和非标签药物治疗后，我们概述了与脆性X综合征相关的行为特征在发育过程中如何在实验动物中建模：我们回顾了迄今为止的进展，讨论了脆性X综合征动物模型中的行为表型分析对于确定潜在治疗方法的重要性，并讨论了该研究领域的注意事项和未来方向。
