THE NHLBI BAY AREA FUNCTIONAL GENOMICS COMSORTIUM

NHLBI 湾区功能基因组学协会

• 批准号: 6291274
• 负责人: William C. SKARNES
• 金额: $ 58.76万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6291274
• 关键词: biotechnology; blood lipoprotein metabolism; cardiopulmonary disease; clone cells; cooperative study; developmental genetics; embryonic stem cell; functional /structural genomics; gene induction /repression; gene targeting; genetically modified animals; heart; in situ hybridization; laboratory mouse; lung; microarray technology; molecular biology information system; training

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.

NHLBI海湾地区功能基因组学联盟将使用基因陷阱载体 在小鼠胚胎干细胞（ES）中植入数千个基因， 它们可自由获得以产生敲除小鼠。 在 初步研究，定制的基因陷阱载体已被用于捕获超过 500个小鼠基因，其中一些是全新的，许多对应于 未知函数 大约150个“被困”的ES细胞克隆已经被克隆。 通过生殖系传播，对基因敲除小鼠的研究 我们已经发现了一些全新的基因， 在心肺发育和疾病中。 该联盟涉及几个领先的旧金山弗朗西斯科湾区的研究 研究机构：大卫格莱斯顿研究所，加州大学， 弗朗西斯科和加州大学伯克利分校。 该企业集团 组织成九个组成部分：（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)基因表达谱和分析，（5）肺肿瘤的小鼠资源 疾病，（6）脂质代谢和动脉粥样硬化的小鼠资源，（7）小鼠 心脏病发展资源，（8）心脏病基因组学 教育;（9）行政管理。 联合体的主要目标（对应于组件1）是使用 定制基因陷阱载体，每年在ES中捕获至少2，500个基因 细胞 每一个“被困”的ES细胞系都将在联盟的网站上公布 （genetrap.org），并将免费分发给研究界， 制造基因敲除小鼠的目的。 第二目标（对应于 组分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，DNA微阵列表达谱， 原位杂交研究。 第三个目标（对应于组件 5-7)是选择一些ES细胞克隆用于生产基因敲除小鼠， 为了了解与心肺发育有关的基因， 和疾病 该联盟的资源将免费分发给任何 感兴趣的研究人员，并应提供催化剂，为许多不同的 NHLBI资助的研究项目。