KOMP2 Annual meeting: The BCM Knockout Mouse Production and Phenotyping Project (BCM KOMP2)

国际老鼠表型鉴定联盟(IMPC)的目标是开发零等位基因资源 小鼠基因组中每一个编码蛋白质的基因的序列，通过标准化、广泛的 表型，对每个目标基因的生物学功能进行分类。美国国立卫生研究院资助的基因敲除小鼠 表型项目(KOMP2)已经支持了空等位基因产生和表型的前两个阶段， 贡献了IMPC制造和表征的一半以上的零等位基因系。此应用程序 描述了贝勒医学院(BCM)在第三阶段继续作为KOMP2网站的计划 资金问题。我们建议培育、冷冻保存和表型为空的600蛋白编码等位基因小鼠品系 基因。我们已经开发了一种生物信息学方法来识别已知或推定的基因并确定其优先顺序 人类疾病关联，但很少到没有体内零等位基因小鼠品系生产的功能注释。 我们将使用已建立的CRISPR基因组编辑方法和质量来生成和验证空等位基因 控制程序，使用公认的技术冷冻保存所有零等位基因系，并将种质传递到 面向社区分发的MMRRC存储库。这些零等位基因系代表了黄金标准资源 对科学界来说，也是未来研究和翻译研究的重要基础。我们会 利用我们已建立的管道对所有突变品系进行广泛、标准化的成体表型鉴定 并在胚胎表型鉴定管道中评估纯合子致死系和亚存活系。表型分型 我们产生的数据将为哺乳动物生物学和遗传基础提供基本的新见解 人类疾病的威胁。所有等位基因和表型数据将实时提交给数据协调中心， 确保所有生物医学数据迅速传播到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和 当新的方法出现时，采用来自社区的新方法。BCM KOMP2团队已经建立了 专业知识、经验和资源，以高效、经济的方式实现提议的第3阶段目标 举止。

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 communitywide 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.