Inducible, dose-adjustable and time-restricted reconstitution of STAT1 deficiency in vivo.

Signal transducer and activator of transcription (STAT) 1 is a key player in interferon (IFN) signaling, essential in mediating host defense against viruses and other pathogens. STAT1 levels are tightly regulated and loss- or gain-of-function mutations in mice and men lead to severe diseases. We hav...

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Autores principales:	Nicole R Leitner, Caroline Lassnig, Rita Rom, Susanne Heider, Zsuzsanna Bago-Horvath, Robert Eferl, Simone Müller, Thomas Kolbe, Lukas Kenner, Thomas Rülicke, Birgit Strobl, Mathias Müller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6fd3c0b5cb514c1389f90ac6c5a95fc6
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spelling	oai:doaj.org-article:6fd3c0b5cb514c1389f90ac6c5a95fc62021-11-18T08:35:10ZInducible, dose-adjustable and time-restricted reconstitution of STAT1 deficiency in vivo.1932-620310.1371/journal.pone.0086608https://doaj.org/article/6fd3c0b5cb514c1389f90ac6c5a95fc62014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24489749/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Signal transducer and activator of transcription (STAT) 1 is a key player in interferon (IFN) signaling, essential in mediating host defense against viruses and other pathogens. STAT1 levels are tightly regulated and loss- or gain-of-function mutations in mice and men lead to severe diseases. We have generated a doxycycline (dox) -inducible, FLAG-tagged Stat1 expression system in mice lacking endogenous STAT1 (i.e. Stat1(ind) mice). We show that STAT1 expression depends on the time and dose of dox treatment in primary cells and a variety of organs isolated from Stat1(ind) mice. In bone marrow-derived macrophages, a fraction of the amount of STAT1 present in WT cells is sufficient for full expression of IFN-induced genes. Dox-induced STAT1 established protection against virus infections in primary cells and mice. The availability of the Stat1(ind) mouse model will enable an examination of the consequences of variable amounts of STAT1. The model will also permit the study of STAT1 dose-dependent and reversible functions as well as of STAT1's contributions to the development, progression and resolution of disease.Nicole R LeitnerCaroline LassnigRita RomSusanne HeiderZsuzsanna Bago-HorvathRobert EferlSimone MüllerThomas KolbeLukas KennerThomas RülickeBirgit StroblMathias MüllerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e86608 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicole R Leitner Caroline Lassnig Rita Rom Susanne Heider Zsuzsanna Bago-Horvath Robert Eferl Simone Müller Thomas Kolbe Lukas Kenner Thomas Rülicke Birgit Strobl Mathias Müller Inducible, dose-adjustable and time-restricted reconstitution of STAT1 deficiency in vivo.
description	Signal transducer and activator of transcription (STAT) 1 is a key player in interferon (IFN) signaling, essential in mediating host defense against viruses and other pathogens. STAT1 levels are tightly regulated and loss- or gain-of-function mutations in mice and men lead to severe diseases. We have generated a doxycycline (dox) -inducible, FLAG-tagged Stat1 expression system in mice lacking endogenous STAT1 (i.e. Stat1(ind) mice). We show that STAT1 expression depends on the time and dose of dox treatment in primary cells and a variety of organs isolated from Stat1(ind) mice. In bone marrow-derived macrophages, a fraction of the amount of STAT1 present in WT cells is sufficient for full expression of IFN-induced genes. Dox-induced STAT1 established protection against virus infections in primary cells and mice. The availability of the Stat1(ind) mouse model will enable an examination of the consequences of variable amounts of STAT1. The model will also permit the study of STAT1 dose-dependent and reversible functions as well as of STAT1's contributions to the development, progression and resolution of disease.
format	article
author	Nicole R Leitner Caroline Lassnig Rita Rom Susanne Heider Zsuzsanna Bago-Horvath Robert Eferl Simone Müller Thomas Kolbe Lukas Kenner Thomas Rülicke Birgit Strobl Mathias Müller
author_facet	Nicole R Leitner Caroline Lassnig Rita Rom Susanne Heider Zsuzsanna Bago-Horvath Robert Eferl Simone Müller Thomas Kolbe Lukas Kenner Thomas Rülicke Birgit Strobl Mathias Müller
author_sort	Nicole R Leitner
title	Inducible, dose-adjustable and time-restricted reconstitution of STAT1 deficiency in vivo.
title_short	Inducible, dose-adjustable and time-restricted reconstitution of STAT1 deficiency in vivo.
title_full	Inducible, dose-adjustable and time-restricted reconstitution of STAT1 deficiency in vivo.
title_fullStr	Inducible, dose-adjustable and time-restricted reconstitution of STAT1 deficiency in vivo.
title_full_unstemmed	Inducible, dose-adjustable and time-restricted reconstitution of STAT1 deficiency in vivo.
title_sort	inducible, dose-adjustable and time-restricted reconstitution of stat1 deficiency in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6fd3c0b5cb514c1389f90ac6c5a95fc6
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Inducible, dose-adjustable and time-restricted reconstitution of STAT1 deficiency in vivo.

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