Molecular Genetic Mapping of the Mouse Brain

描述(由申请人提供)：我们建议测量宽泛和 大约100个不同区域的定量基因表达谱 成年小鼠大脑的基因表达、解剖、功能和 表型。鼠标是研究许多方面的极佳模型 行为与人类心理健康、神经学和 精神障碍。这项建议的主要目标是建立 影响特定表型和基因区域的基因星座 参与正常和疾病相关过程的大脑。这将是 通过测量小鼠大脑中表达的基因谱系来完成 (4个不同的菌株)，并将这些数据汇编成一个公开可用的 数据库将包括1)详细的方法，2)精确的解剖 信息，3)定量基因表达数据，4)数据工具 询问和分析。 将收集四个不同近交系小鼠的数据：C57BL/6J (用于行为和ENU突变)，C3H/HeJ(许多自发的 突变体)、129SvEv(用于产生用于生产的胚胎干细胞 基因敲除小鼠)和DBA2J(用于研究成瘾和焦虑)。我们打算 来检验基因表达差异是导致 大脑结构正常的小鼠品系的行为差异。基因 将使用高密度寡核苷酸阵列获得表达数据 允许同时测量10,000个以上的mRNA丰度 基因和EST，由使用cdna微阵列的研究补充，Northern blots 和定量RT-PCR(Taqman)。结果将被合并到一个 链接的定量基因表达数据、菌株和关系数据库 解剖信息、解剖方案以及组织和切片图像 将公之于众，供研究界使用。数据库 将使用大脑区域特定基因表达信息来生成 关于相关基因、途径和机制的新假说 与脑功能和相关病理相关的表型调节 这会导致精神健康和其他障碍。

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.