THE NHLBI BAY AREA FUNCTIONAL GENOMICS COMSORTIUM

NHLBI-Bay Area功能基因组学联盟将使用基因陷阱载体 灭活小鼠胚胎干细胞中的数千个基因并使其 它们可以免费用于产生基因敲除小鼠。在……里面 初步研究表明，定制的基因陷阱载体已经被用来捕获超过 500个小鼠基因，有些是完全新的，许多对应于 未知函数。大约150个被困住的ES细胞克隆已经被 通过生殖系传播，对基因敲除小鼠的研究 已经导致了完全新的重要基因的识别 在心肺发育和疾病方面。 该联盟涉及几个领先的旧金山湾区研究 机构：J.David Gladstone研究所、加州大学、 旧金山和加州大学伯克利分校。该财团是 分为九个部分：(1)胚胎干细胞中的基因捕获，(2) 预测基因功能的计算方法，(3)原位杂交， (4)基因表达谱与分析；(5)小鼠肺资源 疾病，(6)小鼠脂代谢和动脉粥样硬化资源，(7)小鼠 心肺发育资源，(8)心肺基因组学 教育，以及(9)行政。 联合体的主要目标(对应于构成部分1)是使用 定制基因陷阱载体，每年至少灭活ES中的2500个基因 细胞。每一个被困住的ES细胞系都将在该联盟的网站上公布 (genetRap.org)，并将免费分发给研究社区 制造基因敲除小鼠的目的。第二个目标(对应于 组件2-4)是评估哪些ES细胞系可能是 对了解心肺发育和常见的 心肺疾病。为了实现这一目标，调查人员将 使用计算方法，使用DNA微阵列进行表达谱分析，以及 原位杂交研究。第三个目标(对应于组件 5-7)是选择几个ES细胞克隆来生产基因敲除小鼠， 为了了解与心肺发育有关的基因 和疾病。财团的资源将免费分配给任何 感兴趣的调查者，并应为许多不同的 NHLBI资助的研究项目。

The NHLBI-Bay Area Functional Genomics Consortium will use gene-trap vectors to inactivate thousands of genes in mouse embryonic stem (ES) cells and make them freely available for the purpose of generating knockout mice. In preliminary studies, custom gene-trap vectors have been used to trap more than 500 mouse genes, some completely novel, and many corresponding to ESTs of unknown function. Approximately 150 of the "trapped" ES cell clones have been transmitted through the germline, and studies of the knockout mice have already led to the identification of completely novel genes that are important in cardiopulmonary development and disease. The Consortium involves several leading San Francisco Bay Area research institutions: The J. David Gladstone Institutes, the University of California, San Francisco, and the University of California, Berkeley. The Consortium is organized into nine Components: (1) Gene Trapping in Embryonic Stem Cells, (2) Computational Methods for Predicting Gene Function, (3) In Situ Hybridization, (4) Gene Expression Profiling and Analysis, (5) Mouse Resource for Pulmonary Disease, (6) Mouse Resource for Lipid Metabolism and Atherogenesis, (7) Mouse Resource for Cardiopulmonary Development, (8) Cardiopulmonary Genomics Education, and (9) Administration. The major objective of the Consortium (corresponding to Component 1) is to use custom gene-trap vectors to inactivate at least 2,500 genes per year in ES cells. Each "trapped" ES cell line will be posted on the Consortium's website (genetrap.org) and will be distributed freely to the research community for the purpose of producing knockout mice. A second objective (corresponding to Components 2-4) is to assess which of the ES cell lines is likely to be valuable for understanding cardiopulmonary development and common cardiopulmonary diseases. To achieve this objective, the investigators will use computational approaches, expression profiling with DNA microarrays, and in situ hybridization studies. A third objective (corresponding to Components 5-7) is to select a few ES cell clones for the production of knockout mice, for the purpose of understanding genes involved in cardiopulmonary development and disease. The Consortium's resources will be distributed freely to any interested investigator and should provide a catalyst for many different NHLBI-funded research programs.