The long-term goal of this laboratory is to explore the roles of gene(s) in mental processes as well as the roles of mutations or variants of these genes in the pathogenesis of mental disorders. Recently, haplotypes of G72/G30, a primate-specific gene complex, have been repeatedly reported to associate with schizophrenia. However, neither the neurobiological role of this gene complex nor the mechanism for the involvement of the haplotypes in schizophrenia is well understood. Therefore, it is of significant interest to develop animal models to study the physiological function of this gene complex as well the involvement of its haplotypes in the pathogenesis of schizophrenia. Accordingly, we plan 0 generate two kinds of transgenic mice, in which one harbors the normal G72/G30 gene complex and the other one will harbor specific variants or haplotypes of G72/G30 gene complex derived from schizophrenia patient. We will then systematically characterize these transgenic mice at the molecular, histological, cellular, and behavioral levels. Schizophrenia-like behaviors will be our extensive focus. The results from these studies may not only demonstrate the normal function of G72/G30 gene complex in an experimental system, but may also reveal important evidence to show how the haplotypes contribute to the pathogenesis of schizophrenia. The understanding of this process may constitute a foundation for our efforts on developing novel preventive and therapeutic strategies for patients suffering from schizophrenia.
Schizophrenia is a common and severe mental illness affecting, 1% of the US population. Despite extensive studies, however, the genetic contribution to this illness is not yet clearly elucidated. The results from this proposal may provide important evidence from transgenic mice to show how genetic variants contribute to the pathogenesis of schizophrenia.