Mutant models for genes associated with schizophrenia

Abstract

Schizophrenia is a highly complex and heritable psychiatric disorder in which multiple genes and environmental factors interact to cause the schizophrenia phenotype. A new generation of molecular studies has yielded numerous candidate genes with a putative role in risk for schizophrenia, whereas other genes regulate putative pathophysiological mechanisms. Mutant mice having either deletion (knockout) or insertion (knockin/transgenesis) of schizophrenia risk genes now allow the functional role of these genes to be investigated. In the present mini-review, we outline the advantages and limitations of various approaches to phenotypic assessment of mutant mouse models, including ethologically based methods. Thereafter, we consider recent findings, with a particular focus on, first, dopaminergic and glutamatergic pathophysiological models and, secondly, putative roles for DISC1 (disrupted in schizophrenia 1) and NRG1 (neuregulin 1) as susceptibility genes for schizophrenia. Finally, we identify current challenges associated with the use of genetic mutant models and highlight their potential value for exploring gene–gene and gene–environment interactions in relation to schizophrenia.