Consortium for large-scale production and phenotyping of knockout mice (UM1)

基因敲除小鼠(UM1)大规模生产和表型鉴定联盟 摘要： 国际基因敲除老鼠联盟(IKMC)的长期目标是开发一种 这项研究针对哺乳动物基因组中每一个编码蛋白质的基因在小鼠身上进行了定向突变 社区可以用来阐明基因在人类生物学和疾病中的功能。我们已经组成了一个财团 两个研究所(贝勒医学院和MRC Harwell)。这个应用程序描述了我们计划生成 使用CRISPR/RGN基因组编辑技术对1500个小鼠基因进行零等位基因检测，并使用以下方法验证每个品系 建立质量控制程序。我们将超低温保存所有突变菌株，并将种质交付给MMRRC 储存库。这些突变等位基因代表了更广泛的突变等位基因的黄金标准资源 社区，并为未来的研究和使用小鼠模型的翻译研究奠定了重要基础 已创建。我们将对所有突变系进行广泛的成体表型鉴定，并首次纳入 相当一部分突变体的老化成分，后者涉及额外的测试成分 从12个月起。我们还将评估胚胎中的纯合子致死系和亚存活系。 表型流水线，很明显，小鼠致死(必需)基因和亚存活基因之间存在关系 有人类疾病的基因。所有等位基因和表型数据将实时提交给数据协调中心 中心，确保将所有Bash数据传播给更广泛的生物医学科学界。我们会 继续我们的研发计划，从 从生产到表型。Bash将继续在Cas9 RGN中进行改进试验，以生产更多 复杂的等位基因，同时确保贝勒和贝勒的冷冻保存方法的发展 哈威尔被整合到生产流水线中。我们亦会继续推行各项主要工程，以改善和改善 丰富成人和胚胎表型管道，专注于代谢组学、行为学等领域 表型和家笼监测，目的是提供更复杂和纵向的数据。贝勒 医学院和MRC Harwell拥有成熟的专业知识、经验和资源，可以高效地 并以经济高效的方式实现这一目标。

Consortium for large-scale production and phenotyping of knockout mice (UM1) ABSTRACT: 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. We have formed a consortium of two Institutes (Baylor College of Medicine and MRC Harwell). This application describes our plan to generate null alleles for 1500 mouse genes using CRISPR/RGN genome editing technology and validate each line using established QC procedures. We will cryopreserve all mutant strains and deliver germplasm to the MMRRC repositories. These mutant alleles represent a gold standard resource of mutant alleles for the wider community, and an important foundation for future research and translational studies using the mouse models created. We will perform broad-based adult phenotyping on all mutant lines, and for the first time incorporate an ageing component for a significant fraction of mutants, the latter involving an additional testing component from 12 months onwards. We will also assess homozygous lethal and subviable lines in an embryonic phenotyping pipeline, It is apparent that there is a relationship of mouse lethal (essential) and subviable genes with human disease loci. All allele and phenotype data will be submitted in real time to the Data Coordination Center, ensuring that all of the BasH data is disseminated to the wider biomedical scientific community. We will continue our R&D program to introduce appropriate methodological and technological developments from production to phenotyping. BasH will continue to pilot improvements in Cas9 RGN for the production of more sophisticated alleles, and in parallel ensure that developments in cryopreservation approaches at Baylor and Harwell are integrated into the production pipeline. We will also continue our major projects in improving and enriching the adult and embryo phenotyping pipelines, focusing on areas such as metabolomics, behavioral phenotyping and home cage monitoring, with the aim of providing more complex and longitudinal data. Baylor College of Medicine and MRC Harwell have the established expertise, experience, and resources to efficiently and cost-effectively meet this goal.