Contribution to the completion of Comprehensive Mouse Knockout Resource

为完成综合性小鼠基因敲除资源做出贡献

• 批准号: 7590791
• 负责人: ANDRAS NAGY
• 金额: $ 16.14万
• 依托单位: SINAI HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-07 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7590791
• 关键词: Address; Collection; ES Cell Line; Ensure; European Union; Funding; Gene Mutation; Genes; German population; Goals; Institution; International; Knock-out; Knockout Mice; Laboratories; Learning; Libraries; Medicine; Methods; Missouri; Mus; Mutant Strains Mice; Mutation; Operative Surgical Procedures; Production; Quality Control; Reporter; Request for Applications; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Running; Science; System; Technology; Universities; base; comparative; cost; cost effective; cost efficient; embryonic stem cell; experience; human disease; member; mouse genome; null mutation; programs; tool; transmission process

The overall objective of this project is to further the value of the mouse as a powerful and important tool in the study of human disease through the establishment of a publicly available, comprehensive collection of a fully C57BU6-based null resource knockout embryonic stem cell lines, from which ajibrary of mice containing a null mutation in every gene in the mouse genome can be developed. This application proposes to establish an international consortium of academic institutions comprised of four Canadian (Drs. Naqy. Hicks. Ding and Rancourt). one German (Dr. Wurst) laboratories and the University of Missouri Comparative Medicine Center (Dr. Critser). This consortium was developed to address the NIH RFA (RFA-HG-05-007)for the production of a comprehensive resource of mouse mutants in which every gene in the mouse genome has been knocked out by a null mutation marked with a reporter system of high utility. This consortium fulfills the criteria for an ideal resource in that all of the mutations will be carried on a uniform background strain, C57BL/6, which is the strain most widely utilized by mouse researchers. The unique aspect of this overall proposal is that one laboratory in the consortium (Dr. Nagy's laboratory) has established an exceptional C57BL/6 embryonic stem cell line with a very high germline transmission (-70%). Importantly, this consortium has members which are also part of a Canadian funded project (NORCOMM; Nagy, Hicks, Ding and Rancourt labs) and a European Union funded project (EUCOMM; Wurst lab) to perform high throughput gene mutations in embryonic stems cells. Combining the existing experience and expertise of three major laboratories making null mutations, in combination with the Nagy lab's high germline efficient C57BL/6 embryonic stem cell line and the University of Missouri's expertise in creation of mice and operation of quality control/assurance programs for large NIH-funded resources; will provide a highly efficient and cost effective 'learn" to achieve the goals of this RFA. While several consortium members are involved with similar world-wide efforts to provide a complete library of mouse null imitations, there is no overlap between those projects and this KOMP initiative. In fact, a major strength of this proposal is the vast experience and existing infrastructure in those laboratories. The existing high throughput, low cost methods that are "up and running" in our collective laboratories enable this consortium to accomplish the goals of the KOMP an extremely timely and cost efficient manner. Importantly, because this consortium is comprised of academic groups, in which there are multiple, separately funded, ongoing research projects directly related to the KOMP, we will be able to ensure continuous access to, and application of, the most cutting-edge technologies and science; thereby providing continuous quality improvement over the course of this KOMP. This aspect will ensure the most cost effective methods are applied at each step along the way to completing the core goals of the KOMP.

这个项目的总体目标是进一步提高鼠标作为一种强大而重要的工具的价值， 通过建立一个公开的、全面的 完全基于C57 BU 6的空源敲除胚胎干细胞系， 在小鼠基因组中的每个基因中都含有无效突变的基因。本申请提出 建立一个由四个加拿大学术机构组成的国际财团（Naqy博士。 希克斯Ding和Rancourt）。一家德国（Dr. Wurst）实验室与密苏里州大学比较 医学中心（Dr. Critser）。该联盟旨在解决NIH RFA（RFA-HG-05-007）， 生产一个全面的小鼠突变体资源，其中小鼠基因组中的每个基因， 已经被标记有高实用性的报告系统的无效突变敲除。该财团履行 理想资源的标准在于所有突变将在统一的背景菌株上进行， C57 BL/6，这是小鼠研究人员最广泛使用的品系。这个整体的独特之处在于 一项提议是，联盟中的一个实验室（Nagy博士的实验室）已经建立了一个特殊的实验室。 C57 BL/6胚胎干细胞系具有非常高的生殖系传递（~ 70%）。重要的是这 联合体的成员也是加拿大资助项目的一部分（NORCOMM; Nagy，Hicks，Ding 和Rancourt实验室）和欧盟资助的项目（EUCOMM; Wurst实验室）进行高通量 胚胎干细胞中的基因突变结合现有的经验和专业知识， 实验室进行无效突变，结合Nagy实验室的高生殖系效率C57 BL/6 胚胎干细胞系和密苏里州大学在创造小鼠和操作 大型NIH资助资源的质量控制/保证计划;将提供高效和成本 有效的“学习”，以实现本RFA的目标。虽然有几个财团成员参与了 类似的世界范围内的努力，以提供一个完整的图书馆鼠标零模仿，没有重叠之间 这些项目和KOMP计划。事实上，这项建议的一个主要优点是丰富的经验， 这些实验室的基础设施。现有的高通量、低成本的方法是“向上和向下”的， 在我们的集体实验室中运行”使该联盟能够实现KOMP的目标， 非常及时和具有成本效益的方式。重要的是，由于该联盟由学术界组成， 团体，其中有多个，单独资助，正在进行的研究项目直接相关的 KOMP，我们将能够确保持续获得和应用最前沿的 技术和科学;从而在KOMP过程中提供持续的质量改进。 这一方面将确保最具成本效益的方法适用于每一步沿着的方式完成 KOMP的核心目标。

项目成果

Efficient generation of germ line transmitting chimeras from C57BL/6N ES cells by aggregation with outbred host embryos.

• DOI: 10.1371/journal.pone.0011260
• 发表时间: 2010-06-22
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Gertsenstein M;Nutter LM;Reid T;Pereira M;Stanford WL;Rossant J;Nagy A
• 通讯作者: Nagy A