Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease.
The STAT1 transcription factor is activated in response to many cytokines and growth factors. To study the requirement for STAT1 in vivo, we disrupted the Stat1 gene in embryonic stem (ES) cells and in mice. Stat1(-1-)ES cells were unresponsive to interferon (IFN), but retained responsiveness to leukemia inhibitory factor (LIF) and remained LIF dependent for undifferentiated growth. Stat1(-1-1) animals were born at normal frequencies and displayed no gross developmental defects. However, these animals failed to thrive and were extremely susceptible to viral disease. Cells and tissues from Stat1(-1-) mice were unresponsive to IFN, but remained responsive to all other cytokines tested. Thus, STAT1 appears to be specific for IFN pathways that are essential for viability in the face of otherwise innocuous pathogens.
Durbin
J E
JE
Department of Pathology, New York University School of Medicine, New York 10016, USA.
Hackenmiller
R
R
Simon
M C
MC
Levy
D E
DE
D000818:Animals; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology*; D005260:Female; D018390:Gene Targeting; D006131:Growth Inhibitors / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009894:Opportunistic Infections / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics* / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology / Q000472:pathogenicity; D014777:Virus Diseases / Q000235:genetics* / Q000276:immunology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D007372:Interferons