B6.129-Stat2^tm1Shnd/J

Stock number: 023309
Product name: Stat2^-
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research

Description

This Stat2 (signal transducer and activator of transcription 2) KO strain may be useful for studying the mechanisms of IFN-induced and STAT2-dependant resistance to infections. Recent studies show that STAT2 plays a role in resistance to flaviviruses such as Zika virus (ZIKV), dengue virus (DENV), and West Nile virus (WNV).

Detailed description

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).

Development

A targeting vector was designed to replace exons 2-4 encoding the signal transducer and activator of transcription 2 (Stat2) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to 129Sv/J females. These mice were bred to C57BL/6J mice for at least 7 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Stat2^tm1Shnd
Name: targeted mutation 1, Christian Schindler
MGI accession ID: MGI:2447829
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Stat2
Marker name: signal transducer and activator of transcription 2
Chromosome: 10
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: The gene was disrupted by replacement of exons 1-4 with a PGK-neo cassette via homologous recombination. Absence of gene expression was confirmed by Western blot analysis of primary mouse embryonic fibroblast (PMEF) extracts prepared from homozygous mutant embryos. Stat1 expression was reduced by 50% in Stat2-deficient cells.