Molecular Genetic Mapping of the Mouse Brain

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DESCRIPTION (provided by applicant): We propose to measure broad and quantitative gene expression patterns in approximately 100 different regions of the adult mouse brain in order to relate gene expression, anatomy, function and phenotype. The mouse is an excellent model for studying many aspects of behavior with relevance to a wide range of human mental health, neurologic and psychiatric disorders. The major goal of this proposal is to establish the constellation of genes that influence specific phenotypes and the areas of the brain that are involved in normal and disease related processes. This will be accomplished by measuring the repertoire of genes expressed in the mouse brain (4 different strains), and to assemble these data in a publicly available database that will include 1) detailed methods, 2) precise anatomical information, 3) quantitative gene expression data, and 4) tools for data querying and analysis. Data will be collected for four different inbred strains of mice: C57BL/6J (used for behavior and ENU mutagenesis), C3H/HeJ (a source of many spontaneous mutants), l29SvEv (used for generating embyronic stem cells for producing knockout mice), and DBA2J (used for studying addiction and anxiety). We intend to test the hypothesis that differences in gene expression are responsible for behavioral variance in mouse strains with normal brain architecture. Gene expression data will be obtained using high-density oligonucleotide arrays that enable the simultaneous measurement of mRNA abundance for more than 10,000 genes and ESTs, complemented by studies using cDNA microarrays, northern blots and quantitative RT-PCR (Taqman). The results will be incorporated into a linked, relational database of quantitative gene expression data, strain and anatomical information, dissection protocols and tissue and section images that will be made publicly available for use by the research community. The database of brain region specific gene expression information will be used to generate new hypotheses concerning the genes, pathways and mechanisms involved in modulation of phenotypes related to brain functions and associated pathologies that contribute to mental health and other disorders.