Novel Genetic Models of Autism

自闭症的新遗传模型

基本信息

批准号：
8546632
负责人：
Craig M Powell
金额：
$ 9.98万
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 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8546632
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）是常见的，使影响社会互动，沟通和重复行为的疾病令人衰弱。最近的遗传发现已将突触细胞粘附基因和基因编码其相互作用的蛋白质伴侣在中央突触的基因中鉴定为自闭症谱系疾病的遗传原因。我们建议创建新颖的自闭症模型鼠标线。我们将生产有条件的和可逆的敲除以及全球，完整和同工型自闭症候选基因的特异性敲除，以模仿人类自闭症突变。迄今为止，我们的进步是很大的，因为我们现在已经证明了与自闭症相关的几种突变小鼠模型，从而为我们的研究和一般神经科学界建立了这些界限。现在，我们建议扩大这些新型的自闭症模型小鼠系，并执行初始分子，生化，电生理和行为表征。特别是，我们将测量与这些小鼠系中自闭症谱系障碍中三个核心症状结构域相对应的行为。结果将是自闭症的新型遗传模型小鼠系，模型与自闭症的行为相关性以及使用电生理学对脑功能的初步研究，以了解对皮质突触的影响。