Strain Name:

B6.129-Stat2tm1Shnd/J

Stock Number:

023309

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Availability:

Repository- Live

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 infection.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   19-NOV-13
Specieslaboratory mouse
Generation?+pN1F1 (02-DEC-13)
Generation Definitions
 
Donating Investigator Christian Schindler,   Columbia University

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.

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.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Stat2tm1Shnd/Stat2tm1Shnd

        involves: 129S1/Sv * 129X1/SvJ
  • immune system phenotype
  • abnormal T cell differentiation
    • after a dexamethasone challenge, mutants exhibit a substantial repopulation of the CD4/CD8 double-positive compartment within 2-5 days whereas wild-type mice only show an increase in their CD8+ population   (MGI Ref ID J:66564)
  • increased susceptibility to viral infection
    • mutants succumb to vesicular stomatitis virus (VSV) infection with doses that are about 6 logs lower than in controls   (MGI Ref ID J:66564)
    • primary embryonic fibroblasts infected with VSV produce about 40 times more virus than wild-type cells   (MGI Ref ID J:66564)
    • IFN-alpha treatment afforded no protection against VSV infection as in wild-type   (MGI Ref ID J:66564)
  • hematopoietic system phenotype
  • abnormal T cell differentiation
    • after a dexamethasone challenge, mutants exhibit a substantial repopulation of the CD4/CD8 double-positive compartment within 2-5 days whereas wild-type mice only show an increase in their CD8+ population   (MGI Ref ID J:66564)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Cell Biology Research
Transcriptional Regulation

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines
Inflammation
Intracellular Signaling Molecules

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Stat2tm1Shnd
Allele Name targeted mutation 1, Christian Schindler
Allele Type Targeted (Null/Knockout)
Common Name(s) Stat2-/-;
Strain of Origin129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name Stat2, signal transducer and activator of transcription 2
Chromosome 10
Gene Common Name(s) 1600010G07Rik; AW496480; ISGF-3; P113; RIKEN cDNA 1600010G07 gene; STAT113; expressed sequence AW496480;
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. [MGI Ref ID J:66564]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Neo Melt Curve Analysis, Melt Curve Analysis
Stat2tm1Shnd, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Park C; Li S; Cha E; Schindler C. 2000. Immune response in Stat2 knockout mice. Immunity 13(6):795-804. [PubMed: 11163195]  [MGI Ref ID J:66564]

Additional References

Stat2tm1Shnd related

Alazawi W; Heath H; Waters JA; Woodfin A; O'Brien AJ; Scarzello AJ; Ma B; Lopez-Otalora Y; Jacobs M; Petts G; Goldin RD; Nourshargh S; Gamero AM; Foster GR. 2013. Stat2 loss leads to cytokine-independent, cell-mediated lethality in LPS-induced sepsis. Proc Natl Acad Sci U S A 110(21):8656-61. [PubMed: 23653476]  [MGI Ref ID J:197445]

Farlik M; Reutterer B; Schindler C; Greten F; Vogl C; Muller M; Decker T. 2010. Nonconventional initiation complex assembly by STAT and NF-kappaB transcription factors regulates nitric oxide synthase expression. Immunity 33(1):25-34. [PubMed: 20637660]  [MGI Ref ID J:162548]

Gimeno R; Lee CK; Schindler C; Levy DE. 2005. Stat1 and stat2 but not stat3 arbitrate contradictory growth signals elicited by alpha/beta interferon in T lymphocytes. Mol Cell Biol 25(13):5456-65. [PubMed: 15964802]  [MGI Ref ID J:99124]

Hua L; Yao S; Pham D; Jiang L; Wright J; Sawant D; Dent AL; Braciale TJ; Kaplan MH; Sun J. 2013. Cytokine-dependent induction of CD4+ T cells with cytotoxic potential during influenza virus infection. J Virol 87(21):11884-93. [PubMed: 23986597]  [MGI Ref ID J:203928]

Li J. 2013. JAK-STAT and bone metabolism. JAKSTAT 2(3):e23930. [PubMed: 24069548]  [MGI Ref ID J:202463]

Miyagi T; Gil MP; Wang X; Louten J; Chu WM; Biron CA. 2007. High basal STAT4 balanced by STAT1 induction to control type 1 interferon effects in natural killer cells. J Exp Med 204(10):2383-96. [PubMed: 17846149]  [MGI Ref ID J:126055]

Ousman SS; Wang J; Campbell IL. 2005. Differential regulation of interferon regulatory factor (IRF)-7 and IRF-9 gene expression in the central nervous system during viral infection. J Virol 79(12):7514-27. [PubMed: 15919906]  [MGI Ref ID J:98854]

Perry ST; Buck MD; Lada SM; Schindler C; Shresta S. 2011. STAT2 mediates innate immunity to Dengue virus in the absence of STAT1 via the type I interferon receptor. PLoS Pathog 7(2):e1001297. [PubMed: 21379341]  [MGI Ref ID J:172471]

Stewart CA; Metheny H; Iida N; Smith L; Hanson M; Steinhagen F; Leighty RM; Roers A; Karp CL; Muller W; Trinchieri G. 2013. Interferon-dependent IL-10 production by Tregs limits tumor Th17 inflammation. J Clin Invest :. [PubMed: 24216477]  [MGI Ref ID J:204181]

Wang J; Pham-Mitchell N; Schindler C; Campbell IL. 2003. Dysregulated Sonic hedgehog signaling and medulloblastoma consequent to IFN-alpha-stimulated STAT2-independent production of IFN-gamma in the brain. J Clin Invest 112(4):535-43. [PubMed: 12925694]  [MGI Ref ID J:85154]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB27

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together in a specific pathogen-free (SPF) facility.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   19-NOV-13
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHeterozygous for Stat2tm1Shnd  
$232.00Female or MaleHomozygous for Stat2tm1Shnd  
Price per Pair (US dollars $)Pair Genotype
$464.00Heterozygous for Stat2tm1Shnd x Heterozygous for Stat2tm1Shnd  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHeterozygous for Stat2tm1Shnd  
$301.60Female or MaleHomozygous for Stat2tm1Shnd  
Price per Pair (US dollars $)Pair Genotype
$603.20Heterozygous for Stat2tm1Shnd x Heterozygous for Stat2tm1Shnd  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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