权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular and Cellular Basis of Neurodevelopmental Disorders

神经发育障碍的分子和细胞基础

基本信息

批准号：
10553679
负责人：
Craig M Powell
金额：
$ 65.5万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-10 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10553679
关键词：
16p11.2 Actins Adaptor Signaling Protein Address Affect Animal Genetics Animal Model Area Behavior Behavioral Behavioral Symptoms Binding Proteins Biochemistry Brain CUL3 gene Cell Culture Techniques Code Complex Copy Number Polymorphism DNA Sequence Alteration Data Databases Dendrites Development Disease Disease model Drosophila genus Exhibits FDA approved Face Functional disorder Future Gene Expression Gene Proteins Genes Genetic Genetic Models Head Hela Cells Heterozygote Hippocampus Human In Vitro Intellectual functioning disability Link Macrocephaly Microcephaly Modeling Molecular Monomeric GTP-Binding Proteins Morphology Mus Mutation Nature Neurodevelopmental Disorder Neuronal Dysfunction Neurons PTEN gene Pathway interactions Patients Pharmacotherapy Phenotype Proteins Proteomics Publishing Recurrence Regulation Role Schizophrenia Signal Pathway Social Interaction Structure Synapses Synaptic Transmission Therapeutic Translating Ubiquitination Vertebral column Work Xenopus Zebrafish autism spectrum disorder brain morphology brain size cell motility communication behavior conditional mutant exome sequencing experience gene function gene product innovation interest loss of function mutation mind control mouse model mutant mutant mouse model neurodevelopment neurogenesis neuron development novel repetitive behavior synaptic function therapeutic target transcriptomics treatment strategy ubiquitin ligase ubiquitin-protein ligase

项目摘要

Project Summary/Abstract Neurodevelopmental disorders are common, debilitating disorders including autism, intellectual disability, and perhaps even schizophrenia. Recent genetic findings have identified mutations in multiple genes in various cellular pathways as genetic causes of neurodevelopmental disorders including autism spectrum disorders, intellectual disability, and others. This proposal will characterize novel and innovative genetic mouse models to delineate the function of these genes in the brain. Specifically, the proposal will focus on two genes implicated in either 16p11.2 deletion or autism, both of which are predicted to be involved in overlapping intra- neuronal signaling pathways and regulation of neuronal and synaptic function/development based on preliminary findings. In addition to identifying the neuronal function of these genes in the brain, these studies will identify potential therapeutic strategies for treatment of genetic forms of autism and intellectual disability and possibly other neurodevelopmental disorders. Progress to date is substantial in that two novel mutant mouse models relevant for neurodevelopmental disorders have been established and preliminary characterization of synaptic function, neuronal development, neuronal biochemistry, and neuronal morphology among other aspects of brain function has begun. Unbiased proteomic/transcriptomic approaches to identifying additional, novel downstream targets of these gene products in mammalian brain will generate new hypotheses anticipated to lead to additional potential therapeutic strategies.

项目总结/摘要神经发育障碍是常见的使人衰弱的障碍，包括自闭症、智力障碍和自闭症。甚至可能是精神分裂症最近的遗传学发现已经确定了多种基因的突变，细胞途径作为神经发育障碍包括自闭症谱系障碍的遗传原因，智力残疾和其他。该提案将描述新颖和创新的遗传小鼠模型以描绘这些基因在大脑中的功能。具体来说，该提案将重点关注两个基因与16p11.2缺失或自闭症有关，这两种疾病都被预测参与重叠的细胞内神经元信号传导途径和神经元和突触功能/发育的调节，初步调查结果。除了确定这些基因在大脑中的神经功能外，将确定治疗遗传性自闭症和智力残疾的潜在治疗策略可能还有其他神经发育障碍迄今为止，在两种新突变体已经建立了与神经发育障碍相关的小鼠模型，表征突触功能、神经元发育、神经元生物化学和神经元形态大脑功能的其他方面已经开始。无偏倚的蛋白质组学/转录组学方法此外，这些基因产物在哺乳动物大脑中的新下游靶点将产生新的这些假设预期会导致其他潜在的治疗策略。