The goal of this project is to identify cellular defects that are caused by mutations in genes linked to Autism spectrum disorders (ASD), using the C. elegans neuromuscular junction as a model. In particular, we will test two prominent models for pathophysiological mechanisms in ASD. First, we test the idea that ASD linked genes play a direct role in regulating activity induced gene expression. Second, we will determine if ASD linked genes alter the synaptic targeting of GABAA receptors, thereby altering inhibitory synaptic strength. A critical feature of the genetics of ASD is that mutations conferring risk are nearly always heterozygous in affected individuals, implying that the majority of ASD linked genes are dose sensitive. Thus, we will ask if activity-induced gene expression and synaptic targeting of GABAA receptors are sensitive to copy number variations in ASD linked genes. In addition to testing their potential importance in the pathophysiology of ASD, our Aims address basic mechanisms controlling nervous system development and function.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
