A reporter mouse model to map RIG-I expression and function in vivo
- 1Yale University School of Medicine
Abstract
The cytosolic RNA sensor RIG-I is a critical component of the innate immune response to RNA viruses, yet few tools exist to track RIG-I in vivo. Herein, we report the development of a RIG-I reporter mouse, termed RIG-ImScar, that enables fluorescence imaging and tractable immunoprecipitation of RIG-I in vivo. These mice revealed enrichment of RIG-I expression in circulatory, lymphoid, and mucosal tissues and broad expression across immune cell types. RIG-I itself is upregulated in response to IFN. To distinguish RIG-I sentinel cells, which are programmed to express RIG-I at steady state, from IFN-responder cells, we crossed RIG-ImScar mice with Mx1GFP mice. Blocking IFNAR with a monoclonal antibody showed that basal RIG-I expression in immune cells was largely independent of type I IFN signaling, although Ly6Chi monocytes required IFNAR for RIG-I expression. To probe functional responses in vivo, we intranasally administered a RIG-I-specific agonist, SLR14. Mapping RIG-I expression across the lung identified alveolar macrophages as a critical RIG-I sensor cell population, and depletion of alveolar macrophages, but not neutrophils, slightly impaired lung IFN responses. Together, these findings support the use of the RIG-ImScar model to probe RIG-I dynamics in vivo and predict functional sensor cell populations across tissues.
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BibTeX
@misc{ehrenzeller2026reporter,
title = {{A reporter mouse model to map RIG-I expression and function in vivo}},
author = {S. A. Ehrenzeller and A. C. Hinesley and S. Borunda and S. Liu and D. O. Richards and D.-i. Kwon and T. M. Mehrmann and W. M. Phillbrick and D. T. Thoresen and R. A. Flavell and A. M. Pyle and A. Iwasaki},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.764288},
url = {https://www.biorxiv.org/content/10.64898/2026.11.04.764288v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A reporter mouse model to map RIG-I expression and function in vivo
AU - S. A. Ehrenzeller
AU - A. C. Hinesley
AU - S. Borunda
AU - S. Liu
AU - D. O. Richards
AU - D.-i. Kwon
AU - T. M. Mehrmann
AU - W. M. Phillbrick
AU - D. T. Thoresen
AU - R. A. Flavell
AU - A. M. Pyle
AU - A. Iwasaki
PY - 2026
DA - 2026/11/04
PB - bioRxiv
DO - 10.64898/2026.11.04.764288
UR - https://www.biorxiv.org/content/10.64898/2026.11.04.764288v1
AB - The cytosolic RNA sensor RIG-I is a critical component of the innate immune response to RNA viruses, yet few tools exist to track RIG-I in vivo. Herein, we report the development of a RIG-I reporter mouse, termed RIG-ImScar, that enables fluorescence imaging and tractable immunoprecipitation of RIG-I in vivo. These mice revealed enrichment of RIG-I expression in circulatory, lymphoid, and mucosal tissues and broad expression across immune cell types. RIG-I itself is upregulated in response to IFN. To distinguish RIG-I sentinel cells, which are programmed to express RIG-I at steady state, from IFN-responder cells, we crossed RIG-ImScar mice with Mx1GFP mice. Blocking IFNAR with a monoclonal antibody showed that basal RIG-I expression in immune cells was largely independent of type I IFN signaling, although Ly6Chi monocytes required IFNAR for RIG-I expression. To probe functional responses in vivo, we intranasally administered a RIG-I-specific agonist, SLR14. Mapping RIG-I expression across the lung identified alveolar macrophages as a critical RIG-I sensor cell population, and depletion of alveolar macrophages, but not neutrophils, slightly impaired lung IFN responses. Together, these findings support the use of the RIG-ImScar model to probe RIG-I dynamics in vivo and predict functional sensor cell populations across tissues.
ER -