Molecular Genetic Mapping of the Mouse Brain

描述（由申请人提供）：我们建议衡量广泛和 大约 100 个不同区域的定量基因表达模式 成年小鼠大脑，以便将基因表达、解剖结构、功能和 表型。小鼠是研究许多方面的优秀模型 行为与广泛的人类心理健康、神经系统和 精神疾病。该提案的主要目标是建立 影响特定表型和区域的基因群 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库来完成 （4 种不同的菌株），并将这些数据汇总到公开可用的 数据库将包括 1) 详细的方法，2) 精确的解剖学 信息，3) 定量基因表达数据，以及 4) 数据工具 查询和分析。 将收集四种不同近交系小鼠的数据：C57BL/6J （用于行为和 ENU 诱变）、C3H/HeJ（许多自发的来源） 突变体），l29SvEv（用于生成胚胎干细胞以产生 基因敲除小鼠）和 DBA2J（用于研究成瘾和焦虑）。我们打算 检验基因表达差异导致的假设 具有正常大脑结构的小鼠品系的行为差异。基因 表达数据将使用高密度寡核苷酸阵列获得， 能够同时测量 10,000 多个 mRNA 丰度 基因和 EST，并通过使用 cDNA 微阵列、Northern 印迹的研究进行补充 和定量 RT-PCR (Taqman)。结果将被纳入 定量基因表达数据、菌株和的链接关系数据库 解剖信息、解剖协议以及组织和切片图像 将公开供研究界使用。数据库 大脑区域特定基因表达信息将被用来生成 关于参与的基因、途径和机制的新假设 与大脑功能和相关病理相关的表型调节 导致心理健康和其他疾病。

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.