Inducible, Dose-Adjustable and Time-Restricted Reconstitution of <i>Stat1</i> Deficiency <i>In Vivo</i>

<div><p>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 <i>Stat1</i> expression system in mice lacking endogenous STAT1 (i.e. <i>Stat1^ind</i> 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 <i>Stat1^ind</i> 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 <i>Stat1^ind</i> 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.</p>