Neurobiology of mouse models for human chr 16p11.2 microdeletion and fragile x

描述（由申请人提供）：自闭症是一种普遍的发育障碍，其特征是社交互动和沟通障碍，以及限制重复和刻板的行为或兴趣。脆性X染色体综合征与自闭症具有重叠的临床表现，因此可能具有共同的生化和神经生理特征。识别这些共性对于理解这两种神经发育障碍的发病机制和提供有效的治疗至关重要。人类染色体16p11.2微缺失是自闭症患者最常见的染色体拷贝数变异。我们计划产生携带一个同步区域缺失的小鼠来模拟人类chr16p11.2微缺失表型。我们假设人类chr16p11.2缺失导致突触病理生理与脆性X综合征重叠。这一假设将在我们实验室在脆性X小鼠身上成功进行的一系列实验中得到验证。

DESCRIPTION (provided by applicant): Autism is a pervasive developmental disorder characterized by impairment in social interaction and communication, and restricted repetitive and stereotyped behavior or interest. Fragile X syndrome and autism have overlapping clinical presentation, thus may share common biochemical and neurophysiological features. Identifying these commonalities is vital in understanding the pathogenesis and providing effective therapies for both neurodevelopmental disorders. Human chromosome 16p11.2 microdeletion is the most common chromosome copy number variation (CNV) in autism. We plan to generate mice carrying deletion of a syntenic region to model human chr16p11.2 microdeletion phenotypes. We hypothesize that deletion at human chr16p11.2 causes synaptic pathophysiology that overlaps with Fragile X syndrome. This hypothesis will be tested in a battery of experiments that have been successfully conducted in Fragile X mice in our laboratory. PUBLIC HEALTH RELEVANCE: Autism and Fragile X syndrome are major public health concerns which share some common features in both clinical presentations and pathogenesis. Identifying and characterizing these features is vital in developing effective therapies for both diseases. This can be accomplished by comparing animal models for autism and Fragile X syndrome.