Schizophrenia is a complex brain disease with variable clinical manifestations and different pathogenetic mechanisms. The underlying basis of schizophrenia involves a combination of genetic and epigenetic factors, with several chromosomal loci linked to the disease. Here, we plan to perform global gene expression profiling on a mouse (the chakagrati, ckr) that models certain manifestations of the human condition. To accomplish this goal, we will use oligonucleotide microarray, or chips, for examining gene expression in a high-throughput fashion of the ckr brain. Next, we will mine the data for expression changes and patterns that are related to both ckr and schizophrenia pathology through bioinformatics and statistics. Lastly, alterations in gene expression identified by microarray analysis will be confirmed with conventional methods to establish the validity of the data. It is likely that microarray technology will provide a molecular approach to studying systems neurobiology of the ckr brain and will allow us to comprehensively link certain behavioral profiles of schizophrenia with specific patterns of gene expression changes. Understanding the molecular biology of schizophrenia and model systems will help with the identification of new therapeutic factors, prognosis of disease outcome and therapy response. ? ? ?
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