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Little is known about the developmental origin of autism spectrum disorders (ASDs), but this knowledge will be crucial in developing suitable interventions. Therefore, the goal of this project is to define the critical period in development that produces abnormal behaviors in SHANK3 related autism. The expression of Shank3 is required during the period of rapid synapse development and disruptions in this process produce the core behavioral symptoms of ASD. This project will: 1. Identify the developmental period for Shank3 function that is responsible for producing ASD-like behaviors in Shank3 knockout (KO) mice. 2. Determine the cellular and molecular mechanisms for the role of Shank3 during synapse development. To accomplish this, Shank3 knockout mice will be crossed with another mouse line, which ubiquitously express a tamoxifen-inducible Cre allowing for the inactivation of expression of all Shank3 isoforms in fully developed mice (P60) and mice at an age of rapid synaptogenesis (P10). Mice with depletion of Shank3 at P10 will demonstrate the ASD-like behaviors and molecular phenotypes observed in conventional KO, whereas adult Shank3 KO mice will not. Regardless of the results, this project will advance our understanding of ASD pathophysiology, which will be a crucial step in developing effective interventions.