This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress. The purpose of this FOA is to solicit applications for research projects to make maximum progress toward the goal of producing a null-mutant mouse phenotype resource for each gene in mouse strain C57BL/6, for the purpose of elucidating functional information for each protein-coding gene in the mammalian genome. The specific objectives of this FOA are to generate mutant mouse lines using CRISPR/Cas9 technology, perform phenotyping assays, conduct quality control assessments, cryopreserve germplasm, and make mice and data readily available to the research community. The mouse is the ideal mammalian system in which to produce a functional genomics resource because of the long history and depth of understanding of mouse genetics, the sophistication of assistive reproductive technology in the mouse system, short generation times, and the low cost of working with mice in comparison to other mammals. The recent breakthroughs in CRISPR/Cas9 technology make the mouse an even more cost effective model system and will drive technology of mouse production. The goal of this FOA is to support high-throughput broad based phenotyping of approximately 600 null-mutant mouse lines per year, with an overall goal of 3,000 lines for this five-year project period of the Knockout Mouse Phenotyping Program (KOMP2).