Grant: CIHR Fellowship

The neuropsychiatric disease schizophrenia is a major burden on human health and has no effective therapies. Recent advances in human genetics identified genomic copy number variations (CNVs), such as deletion of the chromosome region 22q11.2, that correlate with a high incidence of schizophrenia and may predispose to the disease. Transgenic mice that harbor the 22q11.2 deletion exhibit circuit and behavioral abnormalities that resemble disease symptoms; however, it is unknown how this CNV generates faulty connections and impairs communication between nerve cells in both species. The goals of this research are to define the cellular defects caused by the 22q11.2 deletion using electrophysiology and live cell imaging, compare them in mouse and human nerve cells, and reverse them in model mice by transplantation of healthy nerve cells derived from human stem cells. We are first to investigate how a CNV linked to a neuropsychiatric disease impairs nerve cell communication in human neurons. Results may establish mice as a valid model for studying 22q11.2 deletion-dependent behavioral changes in schizophrenia and reveal nerve cell transplantation as a viable therapeutic strategy.