SHANK3自闭症动物模型跨物种转录组解析

自闭症谱系障碍是一种高度遗传的神经系统发育性疾病，SHANK3基因的突变会导致严重的自闭症症状。利用与人类自闭症具有高度近似分子缺陷和临床表型的动物模型是研究自闭症发病机制的关键。本项目利用SHANK3突变自闭症动物模型，研究不同脑区的转录组，找出 SHANK3剂量依赖基因，探索其在自闭症发病机制中的作用；为发现合适的药物靶点、开发新药及基因疗法提供更有价值的参考数据。本项目的特色与创新之处在于利用最新的SHANK3突变自闭症猴模型和经典的自闭症鼠模型，研究物种间保守的SHANK3剂量依赖的基因，并揭示这些基因在自闭症发病机制中的作用。

Autism spectrum disorder is a highly inherited developmental disorder of the nervous system. Mutations in SHANK3 gene can lead to moderate to severe autism. Using the animal models with the same genetic defects and clinical phenotypes as human autistic patients is the key to research the pathogenesis of autism. This project aims to use SHANK3 mutant animals to study the transcriptome in different brain areas and identify SHANK3 affected dose-dependent genes. The proposed study will help dissect the role of SHANK3 mutation in the pathogenesis of autism, providing experimental evidence and data to the development of new drugs and gene therapy technology. The novelty of this project lies in the application of new autism monkey model and classic autism mouse model in the exploration of SHANK3 dose-dependent genes among different species and understanding the roles of candidate genes in autism.