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Time: 10:00-11:30 on Thu., Dec. 2, 2021
Venue: Biomedicine Hall,E203
Speaker: Dr. Zhonghua Lu
Host: Dr.Yichang Jia
Title: Phenotyping of SHANK3 Mutant Rodent and Primate Models and Development of Therapeutic Strategies
Mutation of the SHANK3 gene is one of the most common genetic causes for autism spectrum disorder (ASD) in human patients. Using genetically modified rodent and nonhuman primate (NHP) models that carry mutations in the SHANK3 genes, we have characterized their behavioral, cognitive, and physiological phenotypes. SHANK3 mutant macaque monkeys display profound sleep disturbances, motor deficits and increased repetitive behaviors, as well as abnormalities in social behavior and learning. We also found that Shank3 mutant mice have altered fear responses towards predator olfactory cues, suggesting developmental defects in neural circuits processing innate sensory information. Taken together, studies using these animal models have demonstrated a critical role for SHANK3 in core autistic-like behavioral dysfunctions across different animal species. In addition, we are developing AAV-based gene therapy strategies to treat core symptoms using SHANK3 mutant rodent and NHP models.