Mouse models of ZNF804A

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 DESCRIPTION (provided by applicant): This proposal will examine the role of Zfp804a in mouse brain development and behavior as a potential model for biological basis of psychiatric illness. Schizophrenia and other psychiatric illnesses have been recognized to have a familial component for several decades, but genes that underlie these disorders have only recently begun to be identified. In addition to a very few genes with high penetrance in rare families, consortium studies have begun to identify with high confidence larger numbers of genes whose common variants are associated with schizophrenia and bipolar disorder in the general population. While these associated variants individually have only limited predictive power for diagnosis, they nonetheless mark biological bases for the disorder. Understanding the basic mechanisms through which these genes impact brain and mental function may therefore provide key insights into risk and intervention. One of the best-supported and most-replicated associations with schizophrenia and bipolar disorder is ZNF804A, which encodes a protein with a single zinc finger motif and other conserved sequences whose functions are not known. This exploratory proposal aims to create animal models that will (1) test whether the ZNF804A homolog in mouse is required for brain development or normal behavior and (2) facilitate molecular studies to place ZNF804A in cellular and molecular context.