Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway

Marco A. Meraz, J. Michael White, Kathleen C.F. Sheehan, Erika A. Bach, Scott J. Rodig, Anand S. Dighe, Daniel H. Kaplan, Joan K. Riley, Andrew C. Greenlund, Dayle Campbell, Karen Carver-Moore, Raymond N. DuBois, Ross Clark, Michel Aguet, Robert D. Schreiber

Research output: Contribution to journalArticlepeer-review

1433 Scopus citations


The JAK-STAT signaling pathway has been implicated in mediating biologic 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 IFNα or IFNγ 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.

Original languageEnglish (US)
Pages (from-to)431-442
Number of pages12
Issue number3
StatePublished - Feb 9 1996

Bibliographical note

Funding Information:
The authors are grateful for the expert technical assistance of Cora Arthur, Mary Morales, Sarah Ronan (Washington University Medical School) and Gerlinda Stark (University of Zürich, Switzerland). The authors are also grateful to Dr. Emil Unanue and the Center for Immunology at the Department of Pathology of the Washington University Medical School for support of the departmental microinjection facility. The authors wish to thank Dr. Skip Virgin and Mark Heise (Washington University Medical School) for assistance in the viral infection assays; Keith Pinckard and Dr. Ann Gronowski (Washington University Medical School) for helpful discussions; and Dr. George Stark (Cleveland Clinic Research Foundation) and Ian Kerr (Imperial Cancer Research Fund, London) for providing the U3A cell line. The studies conducted in the laboratory of R. D. S. were supported by grants from the National Institutes of Health and Genentech. M. A. was supported by a grant from the Swiss National Science Foundation.


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