A time- and dose-dependent STAT1 expression system

• Main Authors: Painz Ronald, Bokor Marion, Strobl Birgit, Leitner Nicole R, Kolbe Thomas, Rülicke Thomas, Müller Mathias, Karaghiosoff Marina
• Format: Article
• Language: English
• Published: BMC 2006-12-01
• Series: BMC Biotechnology
• Online Access: http://www.biomedcentral.com/1472-6750/6/48

<p>Abstract</p> <p>Background</p> <p>The signal transducer and activator of transcription (STAT) family of transcription factors mediates a variety of cytokine dependent gene regulations. STAT1 has been mainly characterized by its role in interferon (IFN) type I and II signaling and STAT1 deficiency leads to high susceptibility to several pathogens. For fine-tuned analysis of STAT1 function we established a dimerizer-inducible system for STAT1 expression <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>The functionality of the dimerizer-induced STAT1 system is demonstrated <it>in vitro </it>in mouse embryonic fibroblasts and embryonic stem cells. We show that this two-vector based system is highly inducible and does not show any STAT1 expression in the absence of the inducer. Reconstitution of STAT1 deficient cells with inducible STAT1 restores IFNγ-mediated gene induction, antiviral responses and STAT1 activation remains dependent on cytokine stimulation. STAT1 expression is induced rapidly upon addition of dimerizer and expression levels can be regulated in a dose-dependent manner. Furthermore we show that in transgenic mice STAT1 can be induced upon stimulation with the dimerizer, although only at low levels.</p> <p>Conclusion</p> <p>These results prove that the dimerizer-induced system is a powerful tool for STAT1 analysis <it>in vitro </it>and provide evidence that the system is suitable for the use in transgenic mice. To our knowledge this is the first report for inducible STAT1 expression in a time- and dose-dependent manner.</p>