High Throughput Production and Cryopreservation of Knockout Mice

基因敲除小鼠的高通量生产和冷冻保存

• 批准号: 8189110
• 负责人: LEAH RAE B DONAHUE
• 金额: $ 413.3万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-07 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8189110
• 关键词: Throughput; Production; Cryopreservation; Knockout; Mice

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.

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，研究界可以利用该资源来阐明基因在人类生物学和疾病中发挥作用。在此框架内，KOMP^ 计划第一阶段的目标是在五年内产生 2,500 个特征良好的敲除 (KO) 品系。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。该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，能够高效且经济高效地大规模执行所需的中心职能。该中心将利用多种 JAX 资源，包括 JAX Repository（一个主要的社区鼠标资源计划）；生殖科学，菌株冷冻保存和创新研究领域的世界领先者；以及出色的数据管理系统和专业知识。为了实现中心目标，我们将： 1) 从 IKMC ES 细胞生成多达 2,500 个 KO 小鼠系； 2）测试和分析KO小鼠的生存能力和生育能力，并检查每个等位基因的LacZ表达模式； 3) 繁殖、冷冻保存动物和/或种质并将其分发至 KOMP^ 表型中心； 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送到 KOMP^ 数据协调中心数据库 (DCCDB)。该项目与表型中心和 DCCCDB 一起，承诺为科学界提供重要资源。 相关性：小鼠是了解基因功能和开发准确的人类疾病模型的重要动物模型。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。杰克逊实验室拥有出色的专业知识、经验和资源，可以高效且经济高效地实现这一目标。