To define the functions of genes and cell types in vivo, there is no substitute for the power of modifying the mouse germline to generate gene knockouts (KO) and mutants or to express new genes transgenically. For optimal interpretation, genes need to inactivated conditionally or only in certain tissues, or expressed as transgenes in a tissue specific manner in the native genomic context. Using these techniques, investigators worldwide and particularly at Yale, have already been making numerous KO, knockin, transgenic, etc. mouse strains and breeding the modified alleles onto useful genetic backgrounds. These strains, many of which are published, are invaluable resources for research in Rheumatologic diseases, but the maintenance of them is time consuming and expensive, and one cannot envision the endless collection of more and more strains of actively breeding mice. Moreover, infection and breeding problems threaten the existence of many strains, and make the transfer among investigators cumbersome an costly. At the same time, to date the vast majority of engineered mutations have been made by a relatively small number of investigators;these technologies need to be more widely available so that labs that focus on particular genes or processes can have direct access to modifying them, instead of relying on labs that specialize in making KO mice. An important barrier to the technology is in the actual design of KOs and making of constructs as well as construction of BAC constructs via homologous recombination. To address these issues, Core B will take two approaches. First, the Core will provide cryopreservation (and reconstitution of mice from frozen embryos) capabilities for the cost-effective storage of genetically modified mice. Additionally, the core will initiate cryopreservation of sperm and the techniques of IVF for inbred mouse lines. This will produce substantial decreases in costs associated with preservation of mouse strains and will enable distribution both among YRDRCC investigators and outside of Yale. Second, to make modern engineering accessible to the majority of YRDRCC member, the core will provide technological expertise in the generation of KO, conditional KO, knock in, BAC and regulated transgenic constructs. The core will also provide strategies for breeding, genotyping, and initial screening of the resultant mice.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Center Core Grants (P30)
Project #
Application #
Study Section
Special Emphasis Panel (ZAR1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Yale University
New Haven
United States
Zip Code
Gonzalez, David G; Cote, Christine M; Patel, Jaymin R et al. (2018) Nonredundant Roles of IL-21 and IL-4 in the Phased Initiation of Germinal Center B Cells and Subsequent Self-Renewal Transitions. J Immunol 201:3569-3579
Manfredo Vieira, S; Hiltensperger, M; Kumar, V et al. (2018) Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science 359:1156-1161
Greiling, Teri M; Dehner, Carina; Chen, Xinguo et al. (2018) Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Sci Transl Med 10:
Kim, Sang Taek; Choi, Jin-Young; Lainez, Begona et al. (2018) Human Extrafollicular CD4+ Th Cells Help Memory B Cells Produce Igs. J Immunol 201:1359-1372
Weinstein, Jason S; Laidlaw, Brian J; Lu, Yisi et al. (2018) STAT4 and T-bet control follicular helper T cell development in viral infections. J Exp Med 215:337-355
Fistonich, Chris; Zehentmeier, Sandra; Bednarski, Jeffrey J et al. (2018) Cell circuits between B cell progenitors and IL-7+ mesenchymal progenitor cells control B cell development. J Exp Med 215:2586-2599
Gies, Vincent; Schickel, Jean-Nicolas; Jung, Sophie et al. (2018) Impaired TLR9 responses in B cells from patients with systemic lupus erythematosus. JCI Insight 3:
Ip, W K Eddie; Hoshi, Namiko; Shouval, Dror S et al. (2017) Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science 356:513-519
Swartz, Kelsey L; Wood, Scott N; Murthy, Tushar et al. (2017) E2F-2 Promotes Nuclear Condensation and Enucleation of Terminally Differentiated Erythroblasts. Mol Cell Biol 37:
Di Pietro, Caterina; Zhang, Ping-Xia; O'Rourke, Timothy K et al. (2017) Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages. Sci Rep 7:10882

Showing the most recent 10 out of 88 publications