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

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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.