Disruption of the Shank3 gene in a primate model for studying ASD

2015 Scientific Innovations Award
Guoping Feng, Ph.D.
Massachusetts Institute of Technology

Brain disorders represent a great societal burden but are among the least understood of all diseases; for psychiatric disorders in particular, the underlying pathologies are largely unknown and treatment is mostly ineffective. Many brain disorders have a genetic component, and advances in genomic technologies have led to the identification of many risk genes. Understanding how risk genes may cause or contribute to the pathogenesis of psychiatric disorders requires studies of brain function in animal models with genetic alterations that mimic those of human patients. Current animal model studies are largely focused on mice, but mice are imperfect models for many aspects of human biology, particularly neuroscience, given the vast differences in brain and behavior between the two species. The difficulty of modeling complex brain functions and behaviors in mice is an important obstacle both to basic research and to the development of new treatments for human brain disorders. Thus, there is an urgent need to develop animal models that are more close humans in the brain structure and function. In this application, we propose to generate a marmoset (a small primate) model of autism by disrupting the Shank3 gene, which causes autism when mutated in humans. We will use this primate model to further our understanding of neurobiological basis of autism related behaviors. These studies may lead to the identification of novel disease mechanisms and neurobiological targets for drug development foe ASD. More generally, the proposed project, if successful, will establish the marmoset as a primate genetic model for the study of psychiatric disorders.