Leitner Nicole R, Lassnig Caroline, Rom Rita, Heider Susanne, Bago-Horvath Zsuzsanna, Eferl Robert, Müller Simone, Kolbe Thomas, Kenner Lukas, Rülicke Thomas, Strobl Birgit, Müller Mathias
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria.
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.
PLoS One. 2014 Jan 29;9(1):e86608. doi: 10.1371/journal.pone.0086608. eCollection 2014.
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.
信号转导及转录激活因子1（STAT1）是干扰素（IFN）信号传导中的关键因子，在介导宿主抵御病毒及其他病原体方面至关重要。STAT1水平受到严格调控，小鼠和人类中该基因功能的丧失或获得性突变会导致严重疾病。我们在缺乏内源性STAT1的小鼠（即Stat1(ind)小鼠）中构建了一种强力霉素（dox）诱导型、带有FLAG标签的Stat1表达系统。我们发现，在原代细胞以及从Stat1(ind)小鼠分离出的多种器官中，STAT1的表达取决于dox处理的时间和剂量。在骨髓来源的巨噬细胞中，野生型细胞中存在的一部分STAT1量就足以使IFN诱导基因完全表达。dox诱导的STAT1在原代细胞和小鼠中建立了针对病毒感染的保护作用。Stat1(ind)小鼠模型的可用性将有助于研究不同量的STAT1所产生的后果。该模型还将允许研究STAT1的剂量依赖性和可逆性功能，以及STAT1对疾病发生、发展和转归的影响。
