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

摘要 国际小鼠表型鉴定计划(IMPC)和基因敲除小鼠表型鉴定的长期目标 项目(KOMP2)是为小鼠体内每个编码蛋白质的基因开发一种靶向突变资源 研究团体可以用来阐明人类生物学和基因功能的哺乳动物基因组 疾病。在资助的第二阶段(2017-2021年)，贝勒医学院-哈威尔(Bash)财团 任务是使用CRISPR/Cas9技术产生1000个突变小鼠系，这些突变小鼠的表型 零等位基因系，基因和表型数据的质量控制评估，突变株的超低温保存 种质，并向研究界提供小鼠和数据。不过，由于新发疫情的爆发， 严重急性呼吸综合征冠状病毒2型(新冠肺炎)病及其造成的减少 在我们研究所的研究活动中，Bash将不会完成表型分析、数据质量控制 对所有1000个突变系进行评估、超低温保存和分配。为了实现我们的目标，该项目 需要调整时间表，并提供额外的预算支持。这份增刊要求额外的 资助一年完成1000个突变小鼠品系的表型鉴定，进行质量控制评估 数据，种质的冷冻保存，小鼠和数据的分发给研究界。我们会 对所有突变品系进行广泛的成体表型鉴定。我们还将评估纯合子致命性和 胚胎表型流水线中的亚可活系。所有等位基因和表型数据将实时提交 到数据协调中心，确保Bash数据传播到更广泛的生物医学科学 社区。超低温保存的种质将分发给突变小鼠资源和研究中心 在北卡罗来纳大学和密苏里大学。最后，我们将使用CRISPR基因组编辑 生产20个新的零等位基因系的技术，为下一阶段的KOMP2资助做准备。

ABSTRACT The long-term goal of the International Mouse Phenotyping Program (IMPC) and Knockout Mouse Phenotyping Project (KOMP2) 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. In Phase 2 of funding (2017-2021), the Baylor College of Medicine-Harwell (BasH) consortium was tasked with the generation of 1000 mutant mouse lines using CRISPR/Cas9 technology, phenotyping of these null allele lines, quality control assessment of genotype and phenotype data, cryopreservation of mutant strain germplasm, and providing mice and data to the research community. However, due to the outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) and the resulting reduction of research activities at our institutes, BasH will not have completed phenotyping, data quality control assessment, and cryopreservation and distribution of all 1000 mutant lines. To achieve our goals, the project timeline needs to be adjusted and additional budgetary support provided. This supplement requests an additional year of funding to complete phenotyping of 1000 mutant mouse lines, conduct quality control assessment of data, cryopreservation of germplasm, and distribution of mice and data to the research community. We will perform broad-based adult phenotyping on all mutant lines. We will also assess homozygous lethal and subviable lines in an embryonic phenotyping pipeline. All allele and phenotype data will be submitted in real time to the Data Coordination Center, ensuring that BasH data is disseminated to the wider biomedical scientific community. Cryopreserve germplasm will be distributed to the Mutant Mouse Resource and Research Centers at the University of North Carolina and University of Missouri. Finally, we will use CRISPR genome editing technology to produce 20 new null allele lines to prepare for the next phase of KOMP2 funding.