Strain Name:

B6.129S4-Tnfrsf4tm1Nik/J

Stock Number:

012838

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Knock-out Tnfrsf4tm1Nik (also referred to as OX40 or CD134) mice show impaired regulation of T cell number and viability. These mice may be useful for studying the importance of the CD134 molecule in T cell differentiation and responses.

Description

Strain Information

Type Congenic; Mutant Strain; 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)   21-MAR-12
Specieslaboratory mouse
GenerationN14+F11 (11-DEC-13)
Generation Definitions
 
Donating Investigator Nigel Killeen,   Univ of California San Francisco (UCSF)

Description
In Tnfrsf4tm1Nik (also referred to as OX40 or CD134) mice, the knock-out mutation replaces exons 1-4 of the tumor necrosis factor receptor superfamily, member 4 (Tnfrsf4) locus with a floxed neomycin (neo) resistance cassette, abolishing gene function. Homozygous mice are viable, fertile, and normal in size. Tnfrsf4tm1Nik CD4+ T cells demonstrate defects in clonal expansion associated with impaired survival of activated cells. These mice may be useful for studying the importance of the CD134 molecule in T cell differentiation and responses.

Development
A targeting vector was designed to replace exons 1-4 encoding the tumor necrosis factor receptor superfamily, member 4 (Tnfrsf4, originally Ox40) locus with a floxed neomycin resistance (neo) cassette. The construct was electroporated into 129S4/SvJae-derived RF8 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females. These mice were then intercrossed to produce Tnfrsf4-/- mice and were subsequently backcrossed at least 13 generations to C57BL/6 mice. 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

Related Strains

Strains carrying other alleles of Tnfrsf4
012839   B6.129X1(Cg)-Tnfrsf4tm2(cre)Nik/J
View Strains carrying other alleles of Tnfrsf4     (1 strain)

View Strains carrying other alleles of neo     (9 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Immunodeficiency 16; IMD16   (TNFRSF4)
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.

Tnfrsf4tm1Nik/Tnfrsf4tm1Nik

        involves: 129S4/SvJae * C57BL/6
  • immune system phenotype
  • *normal* immune system phenotype
    • primary and secondary lymphoid tissues had normal cellularity, expression of lymphocyte differentiation markers, and presence of germinal centers   (MGI Ref ID J:58979)
    • normal response to infection by: Leishmania major, Nippostrongylus brasiliensis, and Theiler's murine encephalomyelitis   (MGI Ref ID J:58979)
    • normal antibody response to various antigens   (MGI Ref ID J:58979)
    • normal response in delayed-type hypersensitivity reactions using oxazolone   (MGI Ref ID J:58979)
    • abnormal CD4-positive T cell physiology
      • primary and memory responses impaired in response to keyhole limpet hemocyanin immunization: decreased production of antigen-specific CD4+ cells and memory cells and decreased proliferation, decreased production of cytokines (IL2, IFN-gamma, IL5, IL4), at both 7 days and 35 days post-immunization   (MGI Ref ID J:64552)
      • abnormal T-helper 2 physiology
        • impaired ability to mount Th2 response in ovalbumin model of asthma, characterized by lack of production of: IL5, IL4, IgE   (MGI Ref ID J:68588)
    • decreased T cell proliferation
      • in response to anti-CD3 epsilon antibodies, but not in mixed lymphocyte reactions, peptide specific response, or stimulation with staphylococcal enterotoxin B   (MGI Ref ID J:58979)
      • in response to anti-CD3 epsilon antibodies over the course of 5 days   (MGI Ref ID J:64552)
      • corresponding decline in T cell survival over this time   (MGI Ref ID J:64552)
      • declines in IL2 production corresponded to declines in proliferation and survival   (MGI Ref ID J:64552)
    • decreased susceptibility to type I hypersensitivity reaction
      • in response to ovalbumin model of asthma, characterized by decreased lung inflammation, especially with lack of eosinophilia, decreased mucus production, decreased goblet cell hyperplasia and decreased airway hyperreactivity   (MGI Ref ID J:68588)
  • hematopoietic system phenotype
  • abnormal CD4-positive T cell physiology
    • primary and memory responses impaired in response to keyhole limpet hemocyanin immunization: decreased production of antigen-specific CD4+ cells and memory cells and decreased proliferation, decreased production of cytokines (IL2, IFN-gamma, IL5, IL4), at both 7 days and 35 days post-immunization   (MGI Ref ID J:64552)
    • abnormal T-helper 2 physiology
      • impaired ability to mount Th2 response in ovalbumin model of asthma, characterized by lack of production of: IL5, IL4, IgE   (MGI Ref ID J:68588)
  • decreased T cell proliferation
    • in response to anti-CD3 epsilon antibodies, but not in mixed lymphocyte reactions, peptide specific response, or stimulation with staphylococcal enterotoxin B   (MGI Ref ID J:58979)
    • in response to anti-CD3 epsilon antibodies over the course of 5 days   (MGI Ref ID J:64552)
    • corresponding decline in T cell survival over this time   (MGI Ref ID J:64552)
    • declines in IL2 production corresponded to declines in proliferation and survival   (MGI Ref ID J:64552)
View Research Applications

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

Research Tools
Immunology, Inflammation and Autoimmunity Research
      T Cell Receptor Deficiency

neo related

Research Tools
Genetics Research
      Mutagenesis and Transgenesis
      Mutagenesis and Transgenesis: Production of Targeted Mutations (Knockouts), feeder cells for ES cell lines

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tnfrsf4tm1Nik
Allele Name targeted mutation 1, Nigel Killeen
Allele Type Targeted (knock-out)
Common Name(s) CD134-; OX40 KO; OX40-;
Mutation Made By Nigel Killeen,   Univ of California San Francisco (UCSF)
Strain of Origin129S4/SvJae
Expressed Gene neo, neomycin resistance, bacterial
Molecular Note A neomycin cassette was used to replace four exons, which code for the first 143 amino acids of the protein. Activated T cells from homozygous mutant animals lacked expression of Tnfrsf4 as detected by flow cytometry with the OX86 mAb as well as a soluable ligand fusion protein. [MGI Ref ID J:58979]
 
Gene Symbol and Name Tnfrsf4, tumor necrosis factor receptor superfamily, member 4
Chromosome 4
Gene Common Name(s) ACT35; CD134; IMD16; OX40; Ox-40 T-cell antigen; Ox40; TXGP1L; Txgp1; tax-transcriptionally activated glycoprotein 1;

Genotyping

Genotyping Information

Genotyping Protocols

Tnfrsf4tm1Nik, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Pippig SD; Pena-Rossi C; Long J; Godfrey WR; Fowell DJ; Reiner SL; Birkeland ML; Locksley RM; Barclay AN; Killeen N. 1999. Robust B cell immunity but impaired T cell proliferation in the absence of CD134 (OX40). J Immunol 163(12):6520-9. [PubMed: 10586044]  [MGI Ref ID J:58979]

Additional References

Tnfrsf4tm1Nik related

Bansal-Pakala P; Halteman BS; Cheng MH; Croft M. 2004. Costimulation of CD8 T cell responses by OX40. J Immunol 172(8):4821-5. [PubMed: 15067059]  [MGI Ref ID J:89135]

Boettler T; Moeckel F; Cheng Y; Heeg M; Salek-Ardakani S; Crotty S; Croft M; von Herrath MG. 2012. OX40 facilitates control of a persistent virus infection. PLoS Pathog 8(9):e1002913. [PubMed: 22969431]  [MGI Ref ID J:195599]

Burocchi A; Pittoni P; Gorzanelli A; Colombo MP; Piconese S. 2011. Intratumor OX40 stimulation inhibits IRF1 expression and IL-10 production by Treg cells while enhancing CD40L expression by effector memory T cells. Eur J Immunol 41(12):3615-26. [PubMed: 22229156]  [MGI Ref ID J:179655]

Duan W; So T; Croft M. 2008. Antagonism of airway tolerance by endotoxin/lipopolysaccharide through promoting OX40L and suppressing antigen-specific Foxp3+ T regulatory cells. J Immunol 181(12):8650-9. [PubMed: 19050285]  [MGI Ref ID J:142054]

Gough MJ; Ruby CE; Redmond WL; Dhungel B; Brown A; Weinberg AD. 2008. OX40 agonist therapy enhances CD8 infiltration and decreases immune suppression in the tumor. Cancer Res 68(13):5206-15. [PubMed: 18593921]  [MGI Ref ID J:138877]

Gramaglia I; Jember A; Pippig SD; Weinberg AD; Killeen N; Croft M. 2000. The OX40 costimulatory receptor determines the development of CD4 memory by regulating primary clonal expansion J Immunol 165(6):3043-50. [PubMed: 10975814]  [MGI Ref ID J:64552]

Gri G; Piconese S; Frossi B; Manfroi V; Merluzzi S; Tripodo C; Viola A; Odom S; Rivera J; Colombo MP; Pucillo CE. 2008. CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity 29(5):771-81. [PubMed: 18993084]  [MGI Ref ID J:143181]

Griseri T; Asquith M; Thompson C; Powrie F. 2010. OX40 is required for regulatory T cell-mediated control of colitis. J Exp Med 207(4):699-709. [PubMed: 20368580]  [MGI Ref ID J:161661]

Humphreys IR; Loewendorf A; de Trez C; Schneider K; Benedict CA; Munks MW; Ware CF; Croft M. 2007. OX40 costimulation promotes persistence of cytomegalovirus-specific CD8 T Cells: A CD4-dependent mechanism. J Immunol 179(4):2195-202. [PubMed: 17675479]  [MGI Ref ID J:151228]

Jember AG; Zuberi R; Liu FT; Croft M. 2001. Development of allergic inflammation in a murine model of asthma is dependent on the costimulatory receptor OX40. J Exp Med 193(3):387-92. [PubMed: 11157058]  [MGI Ref ID J:68588]

Kroemer A; Xiao X; Vu MD; Gao W; Minamimura K; Chen M; Maki T; Li XC. 2007. OX40 controls functionally different T cell subsets and their resistance to depletion therapy. J Immunol 179(8):5584-91. [PubMed: 17911646]  [MGI Ref ID J:153016]

Lei F; Song J; Haque R; Xiong X; Fang D; Wu Y; Lens SM; Croft M; Song J. 2013. Transgenic expression of survivin compensates for OX40-deficiency in driving Th2 development and allergic inflammation. Eur J Immunol 43(7):1914-24. [PubMed: 23616302]  [MGI Ref ID J:201021]

Magalhaes JG; Rubino SJ; Travassos LH; Le Bourhis L; Duan W; Sellge G; Geddes K; Reardon C; Lechmann M; Carneiro LA; Selvanantham T; Fritz JH; Taylor BC; Artis D; Mak TW; Comeau MR; Croft M; Girardin SE; Philpott DJ. 2011. Nucleotide oligomerization domain-containing proteins instruct T cell helper type 2 immunity through stromal activation. Proc Natl Acad Sci U S A 108(36):14896-901. [PubMed: 21856952]  [MGI Ref ID J:175223]

Piconese S; Valzasina B; Colombo MP. 2008. OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection. J Exp Med 205(4):825-39. [PubMed: 18362171]  [MGI Ref ID J:134000]

Redmond WL; Gough MJ; Weinberg AD. 2009. Ligation of the OX40 co-stimulatory receptor reverses self-Ag and tumor-induced CD8 T-cell anergy in vivo. Eur J Immunol 39(8):2184-94. [PubMed: 19672905]  [MGI Ref ID J:151937]

Redmond WL; Triplett T; Floyd K; Weinberg AD. 2012. Dual anti-OX40/IL-2 therapy augments tumor immunotherapy via IL-2R-mediated regulation of OX40 expression. PLoS One 7(4):e34467. [PubMed: 22496812]  [MGI Ref ID J:187106]

Rogers PR; Song J; Gramaglia I; Killeen N; Croft M. 2001. OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells. Immunity 15(3):445-55. [PubMed: 11567634]  [MGI Ref ID J:71803]

Salek-Ardakani S; Moutaftsi M; Crotty S; Sette A; Croft M. 2008. OX40 drives protective vaccinia virus-specific CD8 T cells. J Immunol 181(11):7969-76. [PubMed: 19017988]  [MGI Ref ID J:142375]

So T; Croft M. 2007. Cutting edge: OX40 inhibits TGF-beta- and antigen-driven conversion of naive CD4 T cells into CD25+Foxp3+ T cells. J Immunol 179(3):1427-30. [PubMed: 17641007]  [MGI Ref ID J:149955]

So T; Soroosh P; Eun SY; Altman A; Croft M. 2011. Antigen-independent signalosome of CARMA1, PKC{theta}, and TNF receptor-associated factor 2 (TRAF2) determines NF-{kappa}B signaling in T cells. Proc Natl Acad Sci U S A 108(7):2903-8. [PubMed: 21282629]  [MGI Ref ID J:169068]

Song A; Song J; Tang X; Croft M. 2007. Cooperation between CD4 and CD8 T cells for anti-tumor activity is enhanced by OX40 signals. Eur J Immunol 37(5):1224-32. [PubMed: 17429847]  [MGI Ref ID J:123581]

Song A; Tang X; Harms KM; Croft M. 2005. OX40 and Bcl-xL promote the persistence of CD8 T cells to recall tumor-associated antigen. J Immunol 175(6):3534-41. [PubMed: 16148096]  [MGI Ref ID J:129686]

Song J; Salek-Ardakani S; Rogers PR; Cheng M; Van Parijs L; Croft M. 2004. The costimulation-regulated duration of PKB activation controls T cell longevity. Nat Immunol 5(2):150-8. [PubMed: 14730361]  [MGI Ref ID J:87871]

Song J; So T; Croft M. 2008. Activation of NF-kappaB1 by OX40 contributes to antigen-driven T cell expansion and survival. J Immunol 180(11):7240-8. [PubMed: 18490723]  [MGI Ref ID J:136337]

Tang Q; Henriksen KJ; Boden EK; Tooley AJ; Ye J; Subudhi SK; Zheng XX; Strom TB; Bluestone JA. 2003. Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J Immunol 171(7):3348-52. [PubMed: 14500627]  [MGI Ref ID J:120383]

Vasilevsky NA; Ruby CE; Hurlin PJ; Weinberg AD. 2011. OX40 engagement stabilizes Mxd4 and Mnt protein levels in antigen-stimulated T cells leading to an increase in cell survival. Eur J Immunol 41(4):1024-34. [PubMed: 21400495]  [MGI Ref ID J:177017]

Vu MD; Xiao X; Gao W; Degauque N; Chen M; Kroemer A; Killeen N; Ishii N; Chang Li X. 2007. OX40 costimulation turns off Foxp3+ Tregs. Blood 110(7):2501-10. [PubMed: 17575071]  [MGI Ref ID J:147020]

Xiao X; Balasubramanian S; Liu W; Chu X; Wang H; Taparowsky EJ; Fu YX; Choi Y; Walsh MC; Li XC. 2012. OX40 signaling favors the induction of T(H)9 cells and airway inflammation. Nat Immunol 13(10):981-90. [PubMed: 22842344]  [MGI Ref ID J:187731]

Xiao X; Gong W; Demirci G; Liu W; Spoerl S; Chu X; Bishop DK; Turka LA; Li XC. 2012. New insights on OX40 in the control of T cell immunity and immune tolerance in vivo. J Immunol 188(2):892-901. [PubMed: 22147766]  [MGI Ref ID J:180889]

Xiao X; Kroemer A; Gao W; Ishii N; Demirci G; Li XC. 2008. OX40/OX40L costimulation affects induction of Foxp3+ regulatory T cells in part by expanding memory T cells in vivo. J Immunol 181(5):3193-201. [PubMed: 18713990]  [MGI Ref ID J:138954]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.
Mating SystemHomozygote x Homozygote         (Female x Male)   21-MAR-12
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 $195.00Female or MaleHomozygous for Tnfrsf4tm1Nik  
Price per Pair (US dollars $)Pair Genotype
$390.00Homozygous for Tnfrsf4tm1Nik x Homozygous for Tnfrsf4tm1Nik  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $253.50Female or MaleHomozygous for Tnfrsf4tm1Nik  
Price per Pair (US dollars $)Pair Genotype
$507.00Homozygous for Tnfrsf4tm1Nik x Homozygous for Tnfrsf4tm1Nik  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Control Information

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

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