Contribution to the completion of Comprehensive Mouse Knockout Resource

该项目的总体目标是进一步提升鼠标作为一种强大而重要的工具的价值 对人类疾病的研究，通过建立一个公开的、全面的 完全基于C57BU6的零资源敲除胚胎干细胞系，从中建立了小鼠的文库 可以开发出在小鼠基因组中每一个基因都含有零突变的基因。此应用程序建议 建立一个国际学术机构联盟，由四名加拿大人(Dr.Naqy. 希克斯。丁和兰库尔)。一家德国(Wurst博士)实验室与密苏里大学比较 医学中心(Critser医生)。该联合体旨在解决NIH RFA(RFA-HG-05-007) 小鼠基因组中每一个基因都能产生一个全面的小鼠突变体资源 已经被一个零突变淘汰了，该突变标记了一个高实用的报告系统。该联合体履行 理想资源的标准是所有突变都将在统一的背景菌株上进行， C57BL/6，这是小鼠研究人员使用最广泛的菌株。这个整体的独特之处在于 建议是财团中的一个实验室(纳吉博士的实验室)已经建立了一个例外的 具有极高生殖系传播率(-70%)的C57BL/6胚胎干细胞株。重要的是，这 该联盟的成员也是加拿大资助的一个项目的一部分(NORCOMM；Nagy，Hicks，Ding 和兰库尔实验室)和欧盟资助的一个项目(EUCOMM；Wurst实验室)，以实现高吞吐量 胚胎干细胞的基因突变。结合三家主要公司的现有经验和专业知识 制造零突变的实验室，结合Nagy实验室的高效种系C57BL/6 胚胎干细胞系和密苏里大学在小鼠创造和手术方面的专业知识 针对NIH资助的大量资源的质量控制/保证计划；将提供高效且成本低廉的 有效的“学习”来实现这个RFA的目标。当几个联盟成员参与到 全球范围内类似的努力提供了一个完整的鼠标空格仿真库，两者之间没有重叠 这些项目和KOMP倡议。事实上，这项建议的一大优势是丰富的经验和 这些实验室的现有基础设施。现有的高吞吐量、低成本的方法 在我们的集体实验室中运行，使该联盟能够实现KOMP和 以极其及时和具有成本效益的方式。重要的是，因为这个联盟是由学术界 小组，其中有多个单独资助的正在进行的研究项目直接与 Komp，我们将能够确保持续访问和应用最尖端的 技术和科学；从而在KOMP的过程中提供持续的质量改进。 这方面将确保在完成过程中的每一步都应用最具成本效益的方法 KOMP的核心目标。

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.