Core B - Mutant Mouse Core

CORE SUMMARY Core B will provide mutant mouse strains required for this IR-PPG. It is an essential Core that will provide PD1/LAG3 floxed mice combined with a unique collection of temporally controlled, lineage-specific Cre mice. AIM 1: To provide the core mutant mice. The Core will be administered from Pitt, with the majority of mutant mouse breeding and procurement outsourced to Taconic under Murine Pathogen Free barrier conditions identical to the majority of its commercial breeding practices. Taconic will generate ~130 mice every month to all research sites using its standard delivery mechanism of a “clean truck shipment system”, thereby avoiding lengthy quarantine and expediting Project research. The total cost per mouse (~$67) is lower than most/all inbred mutant mice from commercial vendors (e.g., CD45.1[JaxBoy]: $74; Pdcd1–/–: $324). Core B will work with Core A to provide all published strains, particularly unique Cre lines, to investigators outside of IR-PPG via Taconic, essentially free (85 investigators thus far), serving as a valuable resource for the scientific community. AIM 2: To generate new mutant mice and combinations. Core B will generate one new mutant mouse strain per year to expand our “immunological toolbox”. We are currently in the process of generating new and more practical Cre and CreERT2 lines that selectively target CD4+ Tconv. Additional strains will be decided with careful consideration and guidelines mediated through Core A and anticipate that we will identify a target gene through the CRISPR screens. These new strains will be generated, validated and banked at Pitt (embryos/sperm) before being established at Taconic and/or shipped directly to the Projects. IR-PPG Interactions: In addition to supporting all three Projects, Core B interacts with Core A to provide easy access to breeding, shipping, and genotyping data, ongoing monitoring, and shipping to outside investigators.