Molecular Genetic Mapping of the Mouse Brain

描述（由申请人提供）：我们建议测量广泛和 在大约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、解剖学、功能和 表型。小鼠是研究许多方面的一个很好的模型， 行为与广泛的人类心理健康，神经和 精神疾病该提案的主要目标是建立 影响特定表型的基因的星座和区域 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），并将这些数据汇集在一个公开可用的 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，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：C57 BL/6 J (used行为和ENU诱变），C3 H/HeJ（许多自发突变的来源）， 突变体）、129 SvEv（用于产生胚胎干细胞， 基因敲除小鼠）和DBA 2 J（用于研究成瘾和焦虑）。我们打算 为了验证基因表达差异是导致 具有正常大脑结构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， 能够同时测量超过10，000个mRNA丰度 基因和ESTs，辅以cDNA微阵列、北方印迹 和定量RT-PCR（Taqman）。结果将纳入一个 定量基因表达数据、菌株和 解剖信息、解剖协议以及组织和切片图像， 将公开提供给研究界使用。数据库 大脑区域特异性基因表达信息将用于生成 新的假说有关的基因，途径和机制参与 调节与脑功能和相关病理学相关的表型 导致心理健康和其他疾病的因素。

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.