MOUSE GENETICS

描述（由申请人提供）：自闭症是一种神经发育障碍， 存在社交缺陷、沟通异常和仪式重复行为。虽然遗传因素的重要性已经得到了很好的证实，但还没有发现导致自闭症或自闭症行为的特定基因。在这个项目中，我们提出了一种方法，使用小鼠模型和基因组规模的基因表达谱来发现基因簇，其表达谱识别分子特征，这些分子特征高度预测社会行为和认知灵活性的自然变异，这些行为与理解自闭症表型明显相关。我们的假设是，自闭症个体表现出的社会和认知行为的变化处于正常遗传控制变化的极端。此外，我们假设行为特征背后的遗传变异是大脑特定区域内独特、稳定的基因表达谱的表现。该项目将导致与自闭症相关的新基因型行为相关性的遗传解剖。我们将通过以下方式实现这一目标：1）在一组不同的小鼠近交系和基因工程模型中表征社会和认知行为表型; 2）为被认为控制目标行为的特定大脑区域生成基因表达谱; 3）确定行为和基因表达之间的关联。

DESCRIPTION (provided by applicant): Autism is a neurodevelopmental disorder defined by the presence of social deficits, communication abnormalities and ritualistic-repetitive behaviors. Although the importance of hereditary factors is well established, no specific genes responsible for autism or autistic behaviors have been identified. In this project we propose an approach using mouse models and genome-scale gene expression profiling to discover clusters of genes whose expression profiles identify molecular signatures that are highly predictive of the natural variation in social behaviors and cognitive flexibility, behaviors of clear relevance to understanding the autistic phenotype. Our hypothesis is that variation in the social and cognitive behaviors manifested by autistic individuals are at the extreme of normal genetically controlled variation. Furthermore, we hypothesize that the genetic variation underlying a behavioral trait is a manifestation of unique, stable gene expression profiles within specific regions of the brain. This project will lead to the genetic dissection of novel genotypebehavior correlations relevant to autism. We will achieve this goal by: 1) characterizing social and cognitive behavior phenotypes in a diverse panel of mouse inbred strains and genetically engineered models; 2) generating gene expression profiles for specific brain regions thought to control the targeted behaviors; and 3) identifying associations between behavior and gene expression.