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 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.
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria.
Nicole R
NR
Leitner
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria ; University Center Biomodels Austria (BIAT), University of Veterinary Medicine Vienna, Vienna, Austria.
Caroline
C
Lassnig
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria.
Rita
R
Rom
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria ; Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.
Susanne
S
Heider
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria ; Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria ; Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria.
Zsuzsanna
Z
Bago-Horvath
Department of Internal Medicine I, Institute for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Robert
R
Eferl
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria.
Simone
S
Müller
University Center Biomodels Austria (BIAT), University of Veterinary Medicine Vienna, Vienna, Austria ; Department IFA-Tulln, Biotechnology in Animal Production, University of Natural Resources and Applied Life Sciences, Tulln, Austria.
Thomas
T
Kolbe
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria ; Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.
Lukas
L
Kenner
Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Vienna, Austria.
Thomas
T
Rülicke
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria.
Birgit
B
Strobl
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria ; University Center Biomodels Austria (BIAT), University of Veterinary Medicine Vienna, Vienna, Austria.
Mathias
M
Müller
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000821:virology; D018188:Cardiovirus Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D004318:Doxycycline / Q000494:pharmacology*; D004686:Encephalomyocarditis virus / Q000276:immunology; D018703:Founder Effect; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D005818:Genetic Engineering; D007372:Interferons / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D061251:Primary Cell Culture; D050794:STAT1 Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013997:Time Factors; D054243:Vesicular Stomatitis / Q000235:genetics* / Q000276:immunology / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007372:Interferons; D004318:Doxycycline