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

Details

Serval ID
serval:BIB_5272DC7AB8EC
Type
Article: article from journal or magazin.
Collection
Publications
Title
Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway.
Journal
Cell
Author(s)
Meraz M.A., White J.M., Sheehan K.C., 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.
ISSN
0092-8674 (Print)
ISSN-L
0092-8674
Publication state
Published
Issued date
1996
Volume
84
Number
3
Pages
431-442
Language
english
Abstract
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.
Keywords
Animals, Base Sequence, Cytokines/pharmacology, Cytopathogenic Effect, Viral, DNA Probes/genetics, DNA-Binding Proteins/genetics, DNA-Binding Proteins/immunology, Female, Gene Targeting, Humans, Interferon-alpha/pharmacology, Interferon-gamma/pharmacology, Lipopolysaccharides/toxicity, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Molecular Sequence Data, Rats, STAT1 Transcription Factor, Signal Transduction/genetics, Signal Transduction/immunology, Trans-Activators/genetics, Trans-Activators/immunology, Vesicular stomatitis Indiana virus/immunology, Vesicular stomatitis Indiana virus/pathogenicity
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:37
Last modification date
20/08/2019 14:07
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