Novel Genetic Models of Autism

自闭症的新遗传模型

基本信息

批准号：
8514664
负责人：
Craig M Powell
金额：
$ 41.53万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8514664
关键词：
22q13 Accounting Address Affect Animal Model Anxiety Autistic Disorder Behavior Behavioral Binding Biochemical Brain Brain Pathology Brain region Candidate Disease Gene Cell Adhesion Child Collaborations Communication Communities Deletion Mutation Development Disease Electrophysiology (science)FDA approved Family Female Fragile X Syndrome Future Genes Genetic Genetic Models Goals Human Human Genetics Intervention Knock-out Knockout Mice Laboratories Lead Link Marriage Measures Mild mental retardation Modeling Molecular Molecular Target Mus Mutation National Institute of Mental Health Neurons Neurosciences PTEN gene Patients Pharmacological Treatment Predisposition Protein Isoforms Proteins Publications Rett Syndrome Role Science Social Interaction Staging Strategic Planning Symptoms Synapses Syndrome Testing Work autism spectrum disorder critical period efficacy testing human FRAP1 protein in vivo kinase inhibitor loss of function mutation male mouse model mutant mouse model neuroligin 1 neuroligin 3 neuropsychiatry new therapeutic target novel recombinase sex social synaptic function tool

项目摘要

DESCRIPTION (provided by applicant): Autism spectrum disorders (ASDs) are common, debilitating disorders affecting social interaction, communication, and repetitive behaviors. Recent genetic findings have identified mutations in synaptic cell adhesion genes and genes encoding their interacting protein partners at central synapses as genetic causes of autism spectrum disorders. We propose to create novel autism model mouse lines. We will produce both conditional and reversible knockouts as well as global, complete and isoform specific knockouts of autism candidate genes to mimic human autism mutations. Our progress to date is substantial in that we have now demonstrated of several mutant mouse models related to autism, thereby establishing these lines for our studies and for the general neuroscience community. We now propose to expand these novel autism model mouse lines and perform initial molecular, biochemical, electrophysiologic and behavioral characterization. In particular, we will measure behaviors corresponding to each of the three core symptom domains in autism spectrum disorder in these mouse lines. The result will be novel genetic model mouse lines of autism, behavioral relevance of the model to autism, and initial studies on brain function using electrophysiology to understand effects on cortical synapses.

描述（由申请人提供）：自闭症谱系障碍 (ASD) 是一种常见的、使人衰弱的疾病，影响社交互动、沟通和重复行为。最近的遗传学研究发现，突触细胞粘附基因和编码中央突触相互作用蛋白伴侣的基因的突变是自闭症谱系障碍的遗传原因。我们建议创建新型自闭症模型小鼠系。我们将产生自闭症候选基因的条件性和可逆性敲除，以及全局、完全和亚型特异性敲除，以模仿人类自闭症突变。迄今为止，我们取得了重大进展，因为我们现在已经证明了几种与自闭症相关的突变小鼠模型，从而为我们的研究和一般神经科学界建立了这些品系。我们现在建议扩展这些新型自闭症模型小鼠系，并进行初步的分子、生化、电生理和行为表征。特别是，我们将测量这些小鼠品系中与自闭症谱系障碍的三个核心症状领域中的每一个相对应的行为。结果将是新的自闭症小鼠遗传模型、该模型与自闭症的行为相关性，以及利用电生理学对大脑功能进行初步研究，以了解对皮质突触的影响。