Schizophrenia is a devastating psychiatric disorder. It affects millions of people who have delusions, reduced feelings of pleasure, dysfunctional ways of thinking and other symptoms. Family studies have shown that schizophrenia has a genetic basis, and recent genomic studies have identified more than 100 different regions in the human genome that can contribute to the development of schizophrenia. It has been largely unclear, however, which genes in these genomic intervals might contribute to schizophrenia and how these genes function.
Summer Thyme and colleagues in the Schier lab used two recent technological advances in zebrafish to address these questions. First, CRISPR/Cas9 allows genome editing to be performed for dozens of genes. Second, phenotypic profiling allows hundreds of larvae to be analyzed for defects in behavior and abnormal brain morphology and activity. By applying these technologies to genes associated with schizophrenia, Thyme et al. mutated 132 genes and analyzed the phenotypes of more than 20,000 larvae. Many of these genes had unknown neurobiological roles, and some had never been studied in any system.