The BCM Knockout Mouse Production and Phenotyping Project (BCM KOMP2)

BCM 敲除小鼠生产和表型项目 (BCM KOMP2)

• 批准号: 10517774
• 负责人: Mary E Dickinson
• 金额: $ 278.57万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10517774
• 关键词: Adopted; Adult; Alleles; Anatomy; Area; Bioinformatics; Biological Process; Biology; CRISPR/Cas technology; Catalogs; Clustered Regularly Interspaced Short Palindromic Repeats; Code; Collaborations; Communities; Cryopreservation; Data; Data Coordinating Center; Defect; Development; Disease; Embryo; Ensure; Essential Genes; Exons; Foundations; Funding; Future; Generations; Genes; Genetic; Goals; Gold; Human; Image; International; Knockout Mice; Machine Learning; Mediating; Medicine; Methodology; Mus; Mutant Strains Mice; Pathway interactions; Phase; Phenotype; Procedures; Production; Program Development; Proteins; Quality Control; Research; Research Personnel; Resources; Role; Site; Standardization; Techniques; Technology; Testing; Time; United States National Institutes of Health; Work; base; behavior test; college; cost effective; data quality; design; experience; gene function; genome editing; human disease; improved; in vivo; informatics infrastructure; insight; large scale production; microCT; mouse genome; mutant; novel; novel strategies; phenotypic data; preclinical study; repository; research study; technology development; tool; translational study

ABSTRACT The goal of the International Mouse Phenotyping Consortium (IMPC) is to develop a resource of null allele lines for every protein-coding gene in the mouse genome and, through standardized, broad-based phenotyping, catalog the biological function of each targeted gene. The NIH-funded Knockout Mouse Phenotyping Project (KOMP2) has supported two previous phases of null allele production and phenotyping, contributing to more than half of the null allele lines made and characterized by the IMPC. This application describes our plan for Baylor College of Medicine (BCM) to continue as a KOMP2 site during a third phase of funding. We propose to produce, cryopreserve, and phenotype null allele mouse lines for 600 protein coding genes. We have developed a bioinformatics approach to identify and prioritize genes with known or putative human disease associations but little-to-no in vivo functional annotation for null allele mouse line production. We will generate and validate null alleles using established CRISPR genome editing approaches and quality control procedures, cryopreserve all null allele lines using accepted techniques, and deliver germplasm to the MMRRC repositories for community- wide distribution. These null allele lines represent a gold standard resource for the scientific community and an important foundation for future research and translational studies. We will utilize our established pipelines to perform broad-based, standardized adult phenotyping on all mutant lines and assess homozygous lethal and subviable lines in an embryonic phenotyping pipeline. The phenotyping data we generate will provide fundamental new insights into mammalian biology as well as the genetic bases of human disease. All allele and phenotype data will be submitted in real time to the Data Coordination Center, ensuring the rapid dissemination of all BCM data to the wider biomedical scientific community. We will continue our production and phenotyping technology development programs, developing our own new approaches and adopting new methodologies from the community as they arise. The BCM KOMP2 team has the established expertise, experience, and resources to meet the proposed phase 3 goals in an efficient and cost-effective manner.

摘要 国际小鼠表型鉴定协会（IMPC）的目标是开发无效等位基因系资源 对于小鼠基因组中的每一个蛋白质编码基因，通过标准化，广泛的表型， 对每个靶基因的生物学功能进行分类。NIH资助的敲除小鼠表型分析项目 （KOMP 2）支持了无效等位基因产生和表型分型的两个先前阶段， 超过一半的无效等位基因系由IMPC制备和表征。此应用程序描述了我们的计划， 贝勒医学院（Baylor College of Medicine）将在第三阶段资助期间继续作为KOMP 2网站。我们建议 生产、冷冻保存和表型无效等位基因小鼠品系，用于600个蛋白质编码基因。我们已经开发 一种生物信息学方法，用于识别和优先考虑与已知或假定的人类疾病相关的基因 但是对于无效等位基因小鼠品系生产几乎没有体内功能注释。我们将生成并验证 使用已建立的CRISPR基因组编辑方法和质量控制程序的无效等位基因，冷冻保存 所有无效等位基因系使用公认的技术，并提供种质资源的MMRRC储存库的社区- 广泛分布。这些无效等位基因系代表了科学界的黄金标准资源， 为未来的研究和转化研究奠定重要基础。我们将利用现有的管道， 对所有突变株系进行基础广泛的标准化成虫表型分析，并评估纯合致死性， 在胚胎表型分析管道中的亚活细胞系。我们生成的表型数据将提供 对哺乳动物生物学以及人类疾病的遗传基础的基本新见解。所有等位基因和 表型数据将以真实的时间提交给数据协调中心，确保快速传播 将所有可识别的数据提供给更广泛的生物医学科学界。我们将继续我们的生产和表型 技术开发计划，开发我们自己的新方法，并采用新的方法， 当社区出现时。ECOKOMP 2团队拥有成熟的专业知识、经验和资源 以有效和具有成本效益的方式实现拟议的第三阶段目标。