HIGH THROUGHPUT PRODUCTION AND CRYOPRESERVATION KNOCKOUT MICE: AIDS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 描述（由申请人提供）：国际基因敲除小鼠联盟（IKMC）的长期目标是为哺乳动物基因组中的每个蛋白质编码基因开发小鼠靶向突变资源，研究界可以使用这些资源来阐明人类生物学和疾病中的基因功能。在此框架内，KOMP计划第一阶段的目标是在五年内产生2，500个良好表征的敲除（KO）系。该计划将在三个功能领域建立一个互动中心系统：KO菌株的生产和初步表型分析;广泛的表型分析;以及该计划的信息学和数据库支持。本申请描述了我们在杰克逊实验室（JAX）建立KO小鼠生产和冷冻保存中心的计划。JAX拥有卓越的专业知识、经验和资源，能够高效、经济地执行所需的大规模中心职能。该中心将利用多个JAX资源，包括JAX Repository，一个主要的社区小鼠资源计划;生殖科学，菌株冷冻保存和创新研究领域的世界领导者;以及出色的数据管理系统和专业知识。为了实现中心的目标，我们将：1）从IKMC ES细胞产生多达2，500个KO小鼠系; 2）测试和分析KO小鼠的存活力和生育力，并检查每个等位基因的LacZ表达模式; 3）繁殖、冷冻保存和将动物和/或种质分发到KOMP表型中心;以及4）通过使用创新技术降低向表型中心提供小鼠和种质的成本。我们将使用JAX现有的可扩展鼠标数据管理和实验室信息管理系统（LIMS）来跟踪所有数据，并将其传达给KOMP^数据协调中心数据库（DCCDB）。与表型中心和DCCDB一起，该项目有望为科学界提供关键资源。 相关性：小鼠是了解基因功能和开发人类疾病精确模型的关键动物模型。作为KOMP计划的一部分，该提案旨在产生多达2500个新的突变小鼠品系，为科学界提供宝贵的资源。杰克逊实验室拥有卓越的专业知识、经验和资源，能够高效、经济地实现这一目标。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. DESCRIPTION (provided by applicant): The long-term goal of the International Knockout Mouse Consortium (IKMC) is to develop a resource of targeted mutations in mice for every protein-coding gene in the mammalian genome that the research community can use to elucidate gene function in human biology and disease. Within this framework, the objective of the first phase of the KOMP^ program is to generate 2,500 well-characterized knockout (KO) lines over five years. The program will establish a system of interactive centers in three functional areas: production and preliminary phenotyping of KO strains; broad-based phenotyping; and informatics and database support for the program. This application describes our plan to establish a KO Mouse Production and Cryopreservation Center at The Jackson Laboratory (JAX). JAX has the exceptional expertise, experience, and resources to efficiently and cost-effectively carry out the Center functions on the large scale required. The Center will leverage multiple JAX resources including the JAX Repository, a major community mouse resource program; Reproductive Sciences, a world leader in strain cryopreservation and innovative research; and outstanding data-management systems and expertise. To meet the Center objectives we will: 1) Generate up to 2,500 KO mouse lines from IKMC ES cells; 2) Test and analyze KO mice for viability and fertility, and examine LacZ expression patterns of each allele; 3) Breed, cryopreserve, and distribute animals and/or germplasm to KOMP^ Phenotyping Centers; and 4) Reduce the cost of providing mice and germplasm to the Phenotyping Centers through the use of innovative technologies. We will use existing, extensible mouse data-management and laboratory information management systems (LIMS) at JAX to track all data and communicate it to the KOMP^ Data Coordination Center Database (DCCDB). Together with the Phenotyping Centers and the DCCDB, this project promises to deliver a critical resource to the scientific community. RELEVANCE: The mouse is a critical animal model for understanding gene function and developing accurate models of human disease. This proposal aims to generate up to 2500 new mutant mouse lines as part of the KOMP Program, providing a valuable resource to the scientific community. The Jackson Laboratory has the outstanding expertise, experience, and resources to efficiently and cost-effectively meet this goal.