Project Summary
Schizophrenia and bipolar disorder are highly heritable diseases that affect millions of people worldwide. However, the molecular basis of these diseases is largely unknown. The Kingsley lab recently identified a large human-specific regulatory insertion in a key calcium channel gene (CACNA1C) that varies in length, structure, and sequence. Strikingly, we find that different versions of this insertion are highly correlated with genetic risk status for schizophrenia and bipolar disorder. The human genetic changes are linked to altered calcium channel gene expression in the cerebellum, a region of the brain extensively studied by the Raymond lab. Interestingly, bipolar disorder patients, and schizophrenia patients and their first degree relatives, perform worse on cerebellum-dependent eye movement tasks than healthy controls, providing a simple behavioral readout that indicates fundamental changes in neural circuits underlying psychiatric disease risk. We will combine the genetics expertise of the Kingsley lab and the neuroscience expertise of the Raymond lab to characterize molecular, cellular, neurophysiological, and behavioral defects in mice engineered to model the risk or protective variants in the human calcium channel gene. We expect this work to elucidate molecular mechanisms that underlie disease risk, and to speed the search for tailored treatments for common psychiatric diseases.
Project Details
Funding Type:
Seed Grant
Award Year:
2019
Lead Researcher(s):