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）：国际基因敲除小鼠财团（IKMC）的长期目标是为哺乳动物基因组中每个蛋白质编码基因的小鼠中有靶向突变的资源开发研究界可以用来阐明基因的蛋白质编码基因人类生物学和疾病的功能。在此框架内，Komp^程序的第一阶段的目的是在五年内生成2,500个良好的淘汰（KO）线路。该计划将在三个功能领域建立一个交互式中心系统：生产和初步表型的KO菌株；基于广泛的表型；以及该程序的信息学和数据库支持。该应用程序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具有出色的专业知识，经验和资源，可以在所需的大规模上有效，成本效益地执行中心功能。该中心将利用多个JAX资源，包括JAX存储库，这是一个主要的社区鼠标资源计划；生殖科学，是菌株冷冻保存和创新研究的世界领导者；以及出色的数据管理系统和专业知识。为了满足中心目标，我们将：1）从IKMC ES细胞中最多生成2500个KO小鼠系； 2）测试和分析KO小鼠的生存力和生育能力，并检查每个等位基因的LACZ表达模式； 3）繁殖，冷冻水果和分配动物和/或种质到科普表型中心； 4）通过使用创新技术来降低向表型中心提供小鼠和种质的成本。我们将使用JAX的现有的，可扩展的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）。该项目与表型中心和DCCDB一起，有望为科学界提供关键的资源。 相关性：小鼠是理解基因功能和开发精确模型人类疾病模型的关键动物模型。该提案旨在作为KOMP计划的一部分生成多达2500种新的突变鼠标线，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，可以有效，成本效益地实现这一目标。