Targeted Disruption of the Stat1 Gene in Mice Reveals Unexpected Physiologic Specificity in the JAK–STAT Signaling Pathway
Open accessAbstract
The JAK-STAT signaling pathway has been implicated in mediating biological responses induced by many cytokines. However, cytokines that promote distinct cellular responses often activate identical STAT proteins, thereby raising the question of how specificity is manifest within this signaling pathway. Here we report the generation and characterization of mice deficient in STAT1. STAT1-deficient mice show no overt developmental abnormalities, but display a complete lack of responsiveness to either IFN alpha or IFN gamma and are highly sensitive to infection by microbial pathogens and viruses. In contrast, these mice respond normally to several other cytokines that activate STAT1 in vitro. These observations document that STAT1 plays an obligate and dedicated role in mediating IFN-dependent biologic responses and reveal an unexpected level of physiologic specificity for STAT1 action.
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The STAT1 knock-out has a specific defect in the interferon-γ response.
“The STAT1 knock-out has a specific defect in the interferon-γ response (46”
From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [46]
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- Authors
- Meraz, M. A., White, J. M., Sheehan, K. C. F., Bach, E. A., Rodig, S. J., Dighe, A. S., Kaplan, D. H., Riley, J. K., Greenlund, A. C., Campbell, D., Carver-Moore, K., DuBois, R. N., Clark, R., Aguet, M., & Schreiber, R. D.
- Affiliations
- Washington University in St. Louis (US)
- Genentech (US)
- Vanderbilt University Medical Center (US)
- Corresponding author
- Schreiber, Robert D
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1996-02
- Volume
- 84
- Issue
- 3
- Pages
- 431-442
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2122506044
- Cited by
- 1,656
- References
- 0
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 33 · 2023: 27 · 2022: 22 · 2021: 37 · 2020: 44 · 2019: 32 · 2018: 26 · 2017: 45 · 2016: 32 · 2015: 26 · 2014: 37 · 2013: 61 · 2012: 53
- FWCI
- 46.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- STAT1, JAK/STAT signaling, STAT1-deficient mice, interferon-alpha, interferon-gamma, antiviral immunity, viral susceptibility, cytokine responsiveness
- MeSH terms
- Animals, Base Sequence, Cytopathogenic Effect, Viral, DNA-Binding Proteins, Female, Humans, Interferon-gamma, Lipopolysaccharides, Male, Mice, Inbred C57BL, Molecular Sequence Data, Vesicular stomatitis Indiana virus, DNA Probes, Signal Transduction, Trans-Activators, Cytokines, Interferon-alpha, Mice, Knockout, Gene Targeting, STAT1 Transcription Factor, Mice, Rats
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