Animal Models for Schizophrenia Via in Utero Gene Transfer: Understanding Roles for Genetic Susceptibility Factors in Brain Development

Genetic disturbances of brain development may underlie the pathophysiology of schizophrenia. Recent advances in molecular neurobiology suggest that some genetic risk factors for schizophrenia have multiple roles in various brain regions depending on the developmental stage. Furthermore, these factors are likely to act synergistically or epistatically in common molecular pathways, possibly contributing to disease pathology. Thus, a technique that can manipulate the expression of more than one gene simultaneously in animal models is necessary to address such molecular pathways. To produce such animal models, in utero gene transfer technique is one useful method. Given that plasmid-based cell-type-specific and inducible gene expression systems are now available, combining these technologies and in utero gene transfer opens a new window to examine the functional role of genetic risk factors for schizophrenia by conducting multiple-gene targeting in a spatial and temporal manner. The utility of animal models produced by in utero gene transfer will also be expected to be evaluated in terms of functional and behavioral outcomes after puberty, which may be associated with schizophrenia pathology.