[HTML][HTML] Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK–STAT signaling pathway

MA Meraz, JM White, KCF Sheehan, EA Bach… - Cell, 1996 - cell.com
Cell, 1996cell.com
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 …
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.
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