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Type of publication: Journal Article
Type of document: Full Paper

Year: 2014

Authors: Leitner, NR; Lassnig, C; Rom, R; Heider, S; Bago-Horvath, Z; Eferl, R; Müller, S; Kolbe, T; Kenner, L; Rülicke, T; Strobl, B; Müller, M

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

Source: PLoS One. 2014; 9(1):e86608



Authors Vetmeduni Vienna:

Bago-Horvath Zsuzsanna Agnes
Kenner Lukas
Kolbe Thomas
Lassnig Caroline
Leitner Nicole
Müller Mathias
Müller Simone
Rom Rita
Rülicke Thomas
Strobl Birgit

Vetmed Research Units
Biomodels Austria
Institut für In-vivo und In-vitro-Modelle
Institute of Animal Breeding and Genetics, Unit of Molecular Genetics


Project(s): Austromouse - Austrian Network for Functional Mouse Genomics

Jak Stat - Signalling from Basis to Disease


Abstract:
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.

Keywords Pubmed: Animals
Bone Marrow Cells/immunology
Bone Marrow Cells/virology
Cardiovirus Infections/genetics*
Cardiovirus Infections/immunology
Cardiovirus Infections/virology
Doxycycline/pharmacology*
Encephalomyocarditis virus/immunology
Founder Effect
Gene Expression Regulation/drug effects*
Gene Expression Regulation/immunology
Genetic Engineering
Interferons/genetics
Interferons/immunology
Macrophages/immunology
Macrophages/virology
Male
Mice
Mice, Transgenic
Primary Cell Culture
STAT1 Transcription Factor/deficiency*
STAT1 Transcription Factor/genetics
STAT1 Transcription Factor/immunology
Signal Transduction
Time Factors
Vesicular Stomatitis/genetics*
Vesicular Stomatitis/immunology
Vesicular Stomatitis/virology
Vesicular stomatitis Indiana virus/immunology


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