Zebrafish Model of Schizophrenia

Background and Objective: Schizophrenia is a heterogeneous, severe psychiatric disorder with a poor life outcome, unsatisfactory treatment options, and poorly understood etiology. With its high heritability, genetic models are a suitable tool for studying this disorder. However, already available animal models do not cover the broad range of schizophrenia symptoms and are not disorder-specific. Recently, a novel high-risk gene (RBM12 ) for schizophrenia had been identified (Steinberg et al., 2017). Using CRISPR/CAS9, three RBM12 zebrafish mutant strains were created. This thesis aimed to validate a schizophrenia-like phenotype in these RBM12 mutants. Methods: The behavior of mutated larval and adult zebrafish was assessed using assays of thigmotaxis, novel tank test, velocity, and sleep. The explored behavioral parameters were based on frequent human symptoms in schizophrenia, including anxiety, positive symptoms, and sleep disturbances. Furthermore, it was attempted to rescue the phenotype with the commonly prescribed antipsychotics haloperidol, chlorpromazine, and the anxiolytic diazepam. Results: The RBM12 mutants exhibited to some extent anxiety-like behavior and fragmented sleep, which could be rescued with antipsychotics and diazepam. The strains differed from each other in symptom type and severity. Conclusion: It can be concluded that RBM12 transgenic zebrafish show at least a partial symptomatology consistent with humans with schizophrenia, providing a novel and promising animal model. However, more research is needed to explore further schizophrenia-like symptoms in this RBM12 model. A selection of suitable assays for this approach is proposed.