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

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1315 Scopus citations

Abstract

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
Pages (from-to)431-442
Number of pages12
JournalCell
Volume84
Issue number3
DOIs
StatePublished - Feb 9 1996

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    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. (1996). Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell, 84(3), 431-442. https://doi.org/10.1016/S0092-8674(00)81288-X