MeCP2转基因食蟹猴所表征的类自闭症行为及种系传递

Autistic-like behaviors by MECP2 transgenic monkeys and germline transmission

自闭症是近年来公众关注度很高的一种神经系统疾病,甲基化CpG结合蛋白2（MeCP2）因其能够在转录水平调节基因表达和操控微小RNA（miRNA）的效应而在自闭症中扮演着重要的角色。当MeCP2因突变而功能缺失时会导致瑞特综合症（Rett syndrome）,而当MeCP2拷贝数过多则会导致一种名为MeCP2重复综合症的自闭症。虽然目前科学家已经构建成功了MeCP2的转基因小鼠,但在这种小鼠模型中无法很好地观察到类似人类自闭症的表型。本研究组通过慢病毒侵染的方法构建了能在神经系统中特异表达人源MeCP2的转基因食蟹猴模型,并通过深度测序检测出了转基因插入位点以及通过免疫印迹（western blot）确证了外源基因的表达。该转基因食蟹猴模型在行动、社交及情绪方面表现出明显的类似自闭症行为,并呈现转基因的种系传递现象。这些结果表明通过基因编辑技术构建非人灵长类模型在脑疾病研究中的重要性。

Autism is a neurological disease with high public concern in recent years. Methyl-CpG binding protein 2（MeCP2） plays an important role in autism for its importance in transcriptional regulation and micro RNA processing. Mutations in MeCP2 gene are found in most of patients with Rett syndrome, duplications of MeCP2-containing genomic segments cause the MeCP2 duplication syndrome, which shares core symptoms with autism spectrum disorders. Although MeCP2 transgenic mice has already been reconstructed, it is still difficult to identify autism-like behaviours in the mouse model of MeCP2 overexpression. In this article we report the lentivirus-based transgenic cynomolgus monkeys expressing human MeCP2 in the brain. Genomic integration sites of the transgenes are characterized by a deepsequencing-based method and expression of the MeCP2 transgene is confirmed by Western blotting. This type of transgenic monkeys exhibits autism-like behaviours in action, social and emotional aspects and shows germline transmission of the transgene. These results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.