Novel Genetic Models of Autism

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，影响社会互动，沟通和重复行为。最近的遗传学研究发现，在突触细胞粘附基因和基因编码的相互作用的蛋白质伴侣在中央突触自闭症谱系障碍的遗传原因的突变。我们建议创建新的自闭症模型小鼠品系。我们将产生条件性和可逆性敲除以及自闭症候选基因的全局、完整和同种型特异性敲除，以模拟人类自闭症突变。迄今为止，我们的进展是实质性的，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的自闭症模型小鼠系，并进行初步的分子，生物化学，电生理和行为表征。特别是，我们将在这些小鼠品系中测量与自闭症谱系障碍的三个核心症状域中的每一个相对应的行为。其结果将是新的自闭症遗传模型小鼠系，该模型与自闭症的行为相关性，以及使用电生理学对大脑功能进行的初步研究，以了解对皮层突触的影响。

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.