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A time- and dose-dependent STAT1 expression system

BACKGROUND: 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 susceptibi...

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Autores principales: Leitner, Nicole R, Strobl, Birgit, Bokor, Marion, Painz, Ronald, Kolbe, Thomas, Rülicke, Thomas, Müller, Mathias, Karaghiosoff, Marina
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770918/
https://www.ncbi.nlm.nih.gov/pubmed/17184522
http://dx.doi.org/10.1186/1472-6750-6-48
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author Leitner, Nicole R
Strobl, Birgit
Bokor, Marion
Painz, Ronald
Kolbe, Thomas
Rülicke, Thomas
Müller, Mathias
Karaghiosoff, Marina
author_facet Leitner, Nicole R
Strobl, Birgit
Bokor, Marion
Painz, Ronald
Kolbe, Thomas
Rülicke, Thomas
Müller, Mathias
Karaghiosoff, Marina
author_sort Leitner, Nicole R
collection PubMed
description BACKGROUND: 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 in vitro and in vivo. RESULTS: The functionality of the dimerizer-induced STAT1 system is demonstrated in vitro 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. CONCLUSION: These results prove that the dimerizer-induced system is a powerful tool for STAT1 analysis in vitro 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.
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spelling pubmed-17709182007-01-17 A time- and dose-dependent STAT1 expression system Leitner, Nicole R Strobl, Birgit Bokor, Marion Painz, Ronald Kolbe, Thomas Rülicke, Thomas Müller, Mathias Karaghiosoff, Marina BMC Biotechnol Research Article BACKGROUND: 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 in vitro and in vivo. RESULTS: The functionality of the dimerizer-induced STAT1 system is demonstrated in vitro 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. CONCLUSION: These results prove that the dimerizer-induced system is a powerful tool for STAT1 analysis in vitro 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. BioMed Central 2006-12-21 /pmc/articles/PMC1770918/ /pubmed/17184522 http://dx.doi.org/10.1186/1472-6750-6-48 Text en Copyright © 2006 Leitner et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Leitner, Nicole R
Strobl, Birgit
Bokor, Marion
Painz, Ronald
Kolbe, Thomas
Rülicke, Thomas
Müller, Mathias
Karaghiosoff, Marina
A time- and dose-dependent STAT1 expression system
title A time- and dose-dependent STAT1 expression system
title_full A time- and dose-dependent STAT1 expression system
title_fullStr A time- and dose-dependent STAT1 expression system
title_full_unstemmed A time- and dose-dependent STAT1 expression system
title_short A time- and dose-dependent STAT1 expression system
title_sort time- and dose-dependent stat1 expression system
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770918/
https://www.ncbi.nlm.nih.gov/pubmed/17184522
http://dx.doi.org/10.1186/1472-6750-6-48
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