In this strain, a neo cassette replaces exons 2-4 of the signal transducer and activator of transcription 2 (Stat2) gene, abolishing gene function. STAT2 is a transcriptional activator induced by cytokines and growth factors. Once activated, STAT2 translocates to the nucleus where it associates with p48 and forms the transcriptional activator complex, interferon-stimulated gene factor 3 (ISGF3). After binding to the IFN stimulated response element (ISRE), ISGF3 is able to activate the transcription of interferon stimulated genes. Homozygous mice are viable and fertile when maintained under SPF conditions. Homozygous Stat2-/- mice fail to mount transcriptional responses to IFNα or IFNβ. These mice show increased susceptibility to vesicular stomatitis virus (VSV) infection and Dengue virus (DENV) infection. They are also more susceptible to LPS-induced sepsis, resulting in mortality due to peritonitis and hepatitis. LPS-induction results in a down-regulation of inflammatory cytokines and chemokines such as TNFα, IL-6, IL-12, IL10, and INFγ.
Recent studies show that STAT2 also plays a role in resistance to other flaviviruses such as Zika virus (ZIKV) and West Nile virus (WNV).
