Strain Name:

B6.129X1-Ebi3tm1Rsb/J

Stock Number:

008691

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
These mutant mice harbor a knockout of the Epstein-Barr virus induced gene 3 (Ebi3) and may be useful in studying Foxp3+ regulatory T cell (Treg) function, IL12 heterodimeric cytokines (such as IL-35 and IL-27), IFNgamma production, and Th1/Th2 immune responses (including inflammatory bowel disease).

Description

Strain Information

Former Names B6.129-Ebi3tm1Rsb/J    (Changed: 05-NOV-08 )
Type Congenic; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHomozygote x Homozygote         (Female x Male)   29-DEC-09
Specieslaboratory mouse
GenerationN10+F7 (28-DEC-12)
Generation Definitions
 
Donating Investigator Richard S Blumberg,   Brigham and Women's Hospital

Description
Mice homozygous for this Ebi3-mutant allele are viable and fertile with the donating investigator reporting no overt autoimmunity or inflammatory disease associated with the mutation. No RNA from the targeted gene is observed in splenocytes isolated from homozygotes. Ebi3-deficiency leads to impaired Treg activity with failure to control homeostatic proliferation. Homozygotes exhibit decreased numbers and function of invariant natural killer T cells (iNKT); stimulated iNKT cells show impaired IL-4 production both in vivo and in vitro. Homozygotes are resistant to oxazolone-induced colitis (mediated primarily by T helper (Th) 2-type cytokine production by iNKT cells), whereas Ebi3-deficiency shows no affect on trinitrobenzene sulfonic acid-induced colitis (a predominantly Th1-mediated colitis model). These Ebi3-mutant strains may be useful in studying Treg function, IL12 heterodimeric cytokines (such as IL-35 and IL-27),IFNgamma production, and Th1/Th2 immune responses (including inflammatory bowel disease).

Of note, Ebi3-mutant mice are also be available on a BALB/c congenic background (see Stock No. 008701).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
The targeting vector was designed to replace exons 2-5 (encoding amino acids 24-228) of the targeted gene with a PGK-Neo cassette. The donating investigators lab reports that the construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and offspring from the resulting chimeric mice were bred to C57BL/6NCrl inbred mice. Ebi3-mutant mice were then backcrossed to C57BL/6NCrl for at least 9 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the current colony.

Control Information

  Control
   005304 C57BL/6NJ (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Ebi3tm1Rsb allele
008701   C.129X1(B6)-Ebi3tm1Rsb/J
View Strains carrying   Ebi3tm1Rsb     (1 strain)

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.

Ebi3tm1Rsb/Ebi3tm1Rsb

        involves: 129X1/SvJ * C57BL/6
  • immune system phenotype
  • abnormal immune system morphology   (MGI Ref ID J:81014)
    • abnormal T-helper 1 cell morphology
      • proportion of Th1 cells increases later in parasitic infections when the infection is resolving   (MGI Ref ID J:97822)
    • abnormal T-helper 2 cell morphology
      • proportion of Th2 is higher early in parasitic infects but not later   (MGI Ref ID J:97822)
      • decreased T-helper 2 cell number
        • lower portion of Th2 cells although levels can be stimulated to normal   (MGI Ref ID J:81014)
    • decreased NK cell number
      • statistically significant reduction in invariant natural killer cells in the liver   (MGI Ref ID J:81014)
      • remaining natural killer cells have a reduced ability to produce IL-4   (MGI Ref ID J:81014)
  • abnormal immune system physiology   (MGI Ref ID J:81014)
    • decreased interleukin-4 secretion
      • after stimulation of CD4+ cells, lower production of IL-4 than in controls   (MGI Ref ID J:81014)
      • serum levels of IL-4 are undetectable after stimulation   (MGI Ref ID J:81014)
    • decreased susceptibility to induced colitis
      • resistant to Th2 mediated oxazolone-induced colitis   (MGI Ref ID J:81014)
      • Th1 mediated colitis proceeds normally   (MGI Ref ID J:81014)
    • increased interferon-gamma secretion
      • unstimulated CD4+ cells produce moderately increased levels of IFN-gamma   (MGI Ref ID J:81014)
      • levels after stimulation are less than controls 2-4 hours after stimulation but reach normal levels at 24 hours   (MGI Ref ID J:81014)
    • increased susceptibility to parasitic infection
      • enhanced susceptibility to Leishmania major at lower physiologically relevant doses   (MGI Ref ID J:97822)
      • larger lesions after L. major infection, 4X the size in controls at 6 week   (MGI Ref ID J:97822)
      • higher parasite burdens at site of infection, peaking at 6 weeks   (MGI Ref ID J:97822)
      • parasite level in spleens reaches 44X that of controls at 7 weeks but decreases after 8 weeks and infection is resolved by 14 weeks   (MGI Ref ID J:97822)
  • digestive/alimentary phenotype
  • decreased susceptibility to induced colitis
    • resistant to Th2 mediated oxazolone-induced colitis   (MGI Ref ID J:81014)
    • Th1 mediated colitis proceeds normally   (MGI Ref ID J:81014)
  • hematopoietic system phenotype
  • abnormal T-helper 1 cell morphology
    • proportion of Th1 cells increases later in parasitic infections when the infection is resolving   (MGI Ref ID J:97822)
  • abnormal T-helper 2 cell morphology
    • proportion of Th2 is higher early in parasitic infects but not later   (MGI Ref ID J:97822)
    • decreased T-helper 2 cell number
      • lower portion of Th2 cells although levels can be stimulated to normal   (MGI Ref ID J:81014)
  • decreased NK cell number
    • statistically significant reduction in invariant natural killer cells in the liver   (MGI Ref ID J:81014)
    • remaining natural killer cells have a reduced ability to produce IL-4   (MGI Ref ID J:81014)
View Research Applications

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

Cancer Research
Genes Regulating Growth and Proliferation
Growth Factors/Receptors/Cytokines

Cell Biology Research
Genes Regulating Growth and Proliferation

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
      genes regulating susceptibility to infectious disease and endotoxin
Growth Factors/Receptors/Cytokines
Immunodeficiency
      Inflammatory bowel disease
      T cell deficiency
      specific T cell deficiency
Inflammation
      Inflammatory bowel disease
Intracellular Signaling Molecules

Internal/Organ Research
Gastrointestinal Defects
      colitis
Lymphoid Tissue Defects
      T cell deficiency

Research Tools
Cancer Research
      T cell deficiency
      specific T cell deficiency
Immunology, Inflammation and Autoimmunity Research
      T cell deficiency
      genes regulating susceptibility to infectious disease and endotoxin
      specific T cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ebi3tm1Rsb
Allele Name targeted mutation 1, Richard Blumberg
Allele Type Targeted (Null/Knockout)
Common Name(s) EBI-3; EBI3-; EBI3tm Birk; Ebi3tm1Birk;
Mutation Made By Richard Blumberg,   Brigham and Women's Hospital
Strain of Origin129X1/SvJ
ES Cell Line NameRW-4
ES Cell Line Strain129X1/SvJ
Gene Symbol and Name Ebi3, Epstein-Barr virus induced gene 3
Chromosome 17
Gene Common Name(s) EBI-3; IL-27; IL-27B; IL27B;
Molecular Note Sequence encompassing exons 2 through 5 was replaced by a neomycin selection cassette inserted by homologous recombination. Northern blot analysis of splenic RNA indicated an absence of normal transcript in homozygous mutant mice. [MGI Ref ID J:81014]

Genotyping

Genotyping Information

Genotyping Protocols

Ebi3tm1Rsb MCA, Melt Curve Analysis
Ebi3tm1Rsb, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Collison LW; Workman CJ; Kuo TT; Boyd K; Wang Y; Vignali KM; Cross R; Sehy D; Blumberg RS; Vignali DA. 2007. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450(7169):566-9. [PubMed: 18033300]  [MGI Ref ID J:127800]

Nieuwenhuis EE; Neurath MF; Corazza N; Iijima H; Trgovcich J; Wirtz S; Glickman J; Bailey D; Yoshida M; Galle PR; Kronenberg M; Birkenbach M; Blumberg RS. 2002. Disruption of T helper 2-immune responses in Epstein-Barr virus-induced gene 3-deficient mice. Proc Natl Acad Sci U S A 99(26):16951-6. [PubMed: 12482940]  [MGI Ref ID J:81014]

Additional References

Ebi3tm1Rsb related

Cobb D; Smeltz RB. 2012. Regulation of proinflammatory Th17 responses during Trypanosoma cruzi infection by IL-12 family cytokines. J Immunol 188(8):3766-73. [PubMed: 22412196]  [MGI Ref ID J:184072]

Collison LW; Chaturvedi V; Henderson AL; Giacomin PR; Guy C; Bankoti J; Finkelstein D; Forbes K; Workman CJ; Brown SA; Rehg JE; Jones ML; Ni HT; Artis D; Turk MJ; Vignali DA. 2010. IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol 11(12):1093-101. [PubMed: 20953201]  [MGI Ref ID J:167328]

Collison LW; Pillai MR; Chaturvedi V; Vignali DA. 2009. Regulatory T cell suppression is potentiated by target T cells in a cell contact, IL-35- and IL-10-dependent manner. J Immunol 182(10):6121-8. [PubMed: 19414764]  [MGI Ref ID J:150297]

Curran MA; Geiger TL; Montalvo W; Kim M; Reiner SL; Al-Shamkhani A; Sun JC; Allison JP. 2013. Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of Eomesodermin. J Exp Med 210(4):743-55. [PubMed: 23547098]  [MGI Ref ID J:198201]

Dokmeci E; Xu L; Robinson E; Golubets K; Bottomly K; Herrick CA. 2011. EBI3 deficiency leads to diminished T helper type 1 and increased T helper type 2 mediated airway inflammation. Immunology 132(4):559-66. [PubMed: 21255010]  [MGI Ref ID J:172100]

Hausding M; Karwot R; Scholtes P; Lehr HA; Wegmann M; Renz H; Galle PR; Birkenbach M; Neurath MF; Blumberg RS; Finotto S. 2007. Lung CD11c+ cells from mice deficient in Epstein-Barr virus-induced gene 3 (EBI-3) prevent airway hyper-responsiveness in experimental asthma. Eur J Immunol 37(6):1663-77. [PubMed: 17506035]  [MGI Ref ID J:123602]

Hu Z; Zhang W; Usherwood EJ. 2013. Regulatory CD8+ T cells associated with erosion of immune surveillance in persistent virus infection suppress in vitro and have a reversible proliferative defect. J Immunol 191(1):312-22. [PubMed: 23733872]  [MGI Ref ID J:205357]

Kochetkova I; Thornburg T; Callis G; Holderness K; Maddaloni M; Pascual DW. 2014. Oral Escherichia coli colonization factor antigen I fimbriae ameliorate arthritis via IL-35, not IL-27. J Immunol 192(2):804-16. [PubMed: 24337375]  [MGI Ref ID J:207334]

Liu JQ; Liu Z; Zhang X; Shi Y; Talebian F; Carl JW Jr; Yu C; Shi FD; Whitacre CC; Trgovcich J; Bai XF. 2012. Increased Th17 and regulatory T cell responses in EBV-induced gene 3-deficient mice lead to marginally enhanced development of autoimmune encephalomyelitis. J Immunol 188(7):3099-106. [PubMed: 22387555]  [MGI Ref ID J:183091]

Liu Z; Liu JQ; Talebian F; Wu LC; Li S; Bai XF. 2013. IL-27 enhances the survival of tumor antigen-specific CD8(+) T cells and programs them into IL-10-producing, memory precursor-like effector cells. Eur J Immunol 43(2):468-79. [PubMed: 23225163]  [MGI Ref ID J:193049]

Matta BM; Raimondi G; Rosborough BR; Sumpter TL; Thomson AW. 2012. IL-27 production and STAT3-dependent upregulation of B7-H1 mediate immune regulatory functions of liver plasmacytoid dendritic cells. J Immunol 188(11):5227-37. [PubMed: 22508931]  [MGI Ref ID J:188752]

Obar JJ; Jellison ER; Sheridan BS; Blair DA; Pham QM; Zickovich JM; Lefrancois L. 2011. Pathogen-induced inflammatory environment controls effector and memory CD8+ T cell differentiation. J Immunol 187(10):4967-78. [PubMed: 21987662]  [MGI Ref ID J:179638]

Rosborough BR; Raich-Regue D; Matta BM; Lee K; Gan B; DePinho RA; Hackstein H; Boothby M; Turnquist HR; Thomson AW. 2013. Murine dendritic cell rapamycin-resistant and rictor-independent mTOR controls IL-10, B7-H1, and regulatory T-cell induction. Blood 121(18):3619-30. [PubMed: 23444404]  [MGI Ref ID J:197572]

Sauer KA; Maxeiner JH; Karwot R; Scholtes P; Lehr HA; Birkenbach M; Blumberg RS; Finotto S. 2008. Immunosurveillance of lung melanoma metastasis in EBI-3-deficient mice mediated by CD8+ T cells. J Immunol 181(9):6148-57. [PubMed: 18941205]  [MGI Ref ID J:140735]

Siebler J; Wirtz S; Frenzel C; Schuchmann M; Lohse AW; Galle PR; Neurath MF. 2008. Cutting edge: a key pathogenic role of IL-27 in T cell- mediated hepatitis. J Immunol 180(1):30-3. [PubMed: 18096999]  [MGI Ref ID J:130899]

Sun J; Dodd H; Moser EK; Sharma R; Braciale TJ. 2011. CD4(+) T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. Nat Immunol 12(4):327-34. [PubMed: 21297642]  [MGI Ref ID J:170347]

Wirtz S; Tubbe I; Galle PR; Schild HJ; Birkenbach M; Blumberg RS; Neurath MF. 2006. Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27. J Exp Med 203(8):1875-81. [PubMed: 16880260]  [MGI Ref ID J:124391]

Zahn S; Wirtz S; Birkenbach M; Blumberg RS; Neurath MF; von Stebut E. 2005. Impaired Th1 responses in mice deficient in Epstein-Barr virus-induced gene 3 and challenged with physiological doses of Leishmania major. Eur J Immunol 35(4):1106-12. [PubMed: 15756639]  [MGI Ref ID J:97822]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.
Mating SystemHomozygote x Homozygote         (Female x Male)   29-DEC-09
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 $199.90Female or MaleHomozygous for Ebi3tm1Rsb  
Price per Pair (US dollars $)Pair Genotype
$399.80Homozygous for Ebi3tm1Rsb x Homozygous for Ebi3tm1Rsb  

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 $259.90Female or MaleHomozygous for Ebi3tm1Rsb  
Price per Pair (US dollars $)Pair Genotype
$519.80Homozygous for Ebi3tm1Rsb x Homozygous for Ebi3tm1Rsb  

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
   005304 C57BL/6NJ (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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