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. This proposal will characterize novel and innovative autism mouse models that allow for brain development to take place with a genetic mutation. These particular models allow for reversal of the mutation at various times during brain development and ultimately in specific brain regions. The goal is to narrow the developmental critical period during which such mutations lead to altered brain function and atypical behavior. This information will allow scientists to focus specifically on the time periods and brain regions critical for generation of atypical behavior. In addition, these studies will substantiate feasibility of genetic and certain pharmacological approaches to treatment of a genetic form of autism. Progress to date is substantial in that the genetically reversible mutant mouse models related to autism have been established and characterization has begun.
It is critical to better understand genetic causes of human autism and to use animal models of such causes to identify treatments. This 5-year R01 renewal proposal capitalizes on significant progress in creating and characterizing animal models of autism that will allow us to rapidly advance this field. Novel genetic animal models have been created that now allow for precise control over genetic mutations and reversal of these genetic mutations at any time during development of the brain and in any brain region allowing extensive characterization of these new models for a complete understanding of when during brain development things go awry and where in the brain things go awry.
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