Abstract：
Fragile X Syndrome (FXS), the most common inherited form of human intellectual disability, is a monogenic neurodevelopmental disorder caused by a loss-of-function mutation of the FMR1 gene. FMR1 is encoding the Fragile X Messenger Ribonucleo Protein (FMRP) an RNA-binding protein that regulates the translation of synaptic proteins. The absence of FMRP expression has many important consequences on synaptic plasticity and function, leading to the FXS clinical phenotype. Over the last decade, a visual neurosensorial phenotype had been described in the FXS patients as well as in the murine model (Fmr1-/ymice), characterized by retinal deficits associated to retinal perception alterations. However, although the transcriptomic profile in the absence of FMRP has been studied in the cerebral part of the central nervous system (CNS), there are no actual data for the retina which is an extension of the CNS. Herein, we investigate the transcriptomic profile of mRNA from whole retinas of Fmr1-/ymice. Interestingly, we found a specific signature of Fmrp absence on retinal mRNA expression with few common genes compared to other brain studies. Gene Ontology on these retinal specific genes demonstrated an enrichment in retinal development genes as well as in synaptic genes. These alterations could be linked to the reported retinal phenotype of the FXS condition. In conclusion, we describe for the first time, retinal-specific transcriptomic changes in the absence of FMRP.
摘要：
脆性X综合征（FXS），人类智力残疾最常见的遗传形式，是由FMR1基因的功能丧失突变引起的单基因神经发育障碍。FMR1编码脆性X信使核糖核酸蛋白（FMRP），这是一种调节突触蛋白翻译的RNA结合蛋白。FMRP表达的缺失对突触可塑性和功能有许多重要影响，导致FXS临床表型。在过去的十年里，在FXS患者以及小鼠模型（Fmr1-/ymice）中已经描述了视觉神经感觉表型，以与视网膜感知改变相关的视网膜缺陷为特征。然而,尽管已经在中枢神经系统（CNS）的大脑部分研究了不存在FMRP的转录组学谱，没有视网膜的实际数据，视网膜是中枢神经系统的延伸。在这里，我们研究了Fmr1-/ymice整个视网膜mRNA的转录组学特征。有趣的是,与其他脑部研究相比,我们在视网膜mRNA表达上发现了Fmrp缺失的特异性特征,且常见基因很少.这些视网膜特异性基因的基因本体论证明了视网膜发育基因以及突触基因的富集。这些改变可能与所报道的FXS病症的视网膜表型有关。总之,我们第一次描述，在没有FMRP的情况下，视网膜特异性转录组的变化。
