- CORE C The Transgenic / Knockout Mouse Core provides a critical means by which the PPG will achieve its goals of understanding TIM-3 function and regulation of TIM-3 expression in cancer, autoimmune disease and chronic infections. This Core will provide PPG investigators with an important and unique collection of mouse strains for these studies. The Core has the expertise with both conventional and conditional transgenic and knockout technology that will enable the generation of novel mouse strains for analyzing TIM-3 function and the regulation of TIM-3 expression in vivo. To facilitate studies of TIM-3 function and TIM-3 expression, the Core also will generate TIM-3 conditional knockout strains by breeding TIM-3fl/fl mice with different Cre-driver strains. Initial priorities will be to breed TIM- 3fl/fl with dLck-cre and FoxP3-Cre. Core C also will breed carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM-1)-/- mice with TIM-3fl/fl x dLck-Cre mice. To enable studies of the cytokine regulation of TIM-3 expression, the Core will breed conditional transcription factor knockout mice with Cre strains of interest, cytokine reporter, and cytokine receptor knockout mice. In addition, Core C has access to FoxP3-GFP knock- in (KI) mice, which enable the visualization of the impact of transcription factors, cytokine/cytokine receptors on expression of TIM-3 on regulatory T cells in vivo. Finally, Core will serve as a repository for new mouse strains generated by the Core. The Transgenic/ Knockout Mouse Core will provide breeding pairs of these strains to PPG investigators as needed.
- CORE C These studies will provide fundamental information about how, where, and when TIM-3 regulates tolerance, autoimmunity, and T cell exhaustion. The results of our studies will have implications for developing new therapies for human malignancies, chronic infection, and autoimmune diseases.
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