Mutant and Transgenic Tools in Modeling Schizophrenia

Schizophrenia is thought to be a polygenic disorder that is associated with considerable phenotypic heterogeneity across patients, including variations in age at onset, diagnostic symptoms and subsequent course of illness. Consequently, the generation of incisive mutant models for this disorder faces substantive challenges. The majority of mutant models for schizophrenia relate to putative pathobiological and pharmacological processes and to the functional roles of the increasingly large and diverse array of genes associated with risk for the disorder. The present review considers the application of mutant animal phenotypes to the study of pathobiological and pharmacological mechanisms thought to be relevant for schizophrenia, particularly in terms of dopaminergic and glutamatergic dysfunction, and to an increasing range of candidate susceptibility genes. We also discuss various technological approaches to the generation of such mutants and highlight the diverse methodologies adopted in phenotypic assessment of these models. Finally, we outline the principal challenges to be faced by researchers engaging in the generation and evaluation of mutant models for schizophrenia and consider possible approaches to identify improved models.