Overview

Also Known As:BALB/c-TRAF1, BALB/c TRAF1

These TRAF1 mutant mice may be useful in studying negative regulation of tumor necrosis factor (TNF) signaling, NF-kB and AP-1 signaling, T cell receptor (TCR)-induced proliferation of T cells, Th2 responses, TRAF1/Bim function in CD8 memory T cell survival, allergic airway diseases and Rheumatoid arthritis, as well as the role of TRAF1 activation in the pathogenesis of lymphomas. Of note, TRAF1 mutant mice are available on either a BALB/c congenic (Stock No. 008074) or C57BL/6 congenic (Stock No. 008076) background.

Donating Investigator

Gloria Pryhuber, University of Rochester

Genetic overview

Genetic Background	Generation

Traf1^tm1Tsi

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Traf1	TNF receptor-associated factor 1

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Research Applications

Apoptosis Research
Cell Biology Research
Cancer Research
Research Tools
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the TRAF1 mutant allele (TRAF1^-/-) are viable and fertile. No protein expression from the targeted gene is observed in CD40-stimulated splenocytes isolated from homozygous mice. Homozygous mice on a BALB/c congenic background (BALB/c-TRAF1^-/-) exhibit acute liver injury and elevated serum liver enzymes following intratracheal TNF-alpha treatment. Furthermore, activated TRAF1^-/- T cells have significantly increased expression of Th2 cytokines (IL-4, IL-5 and IL-13) that elicit enhanced Th2 responses in vivo. BALB/c-TRAF1^-/- T cells exhibit elevated nuclear expression of NFAT-interacting protein (NIP45) and also induce significantly more intense pulmonary inflammation and higher airway hyper-responsiveness in OVA allergic inflammation models. Pulmonary leukocyte recruitment is attenuated following inhalation of lipopolysaccharide in BALB/c-TRAF1^-/- mice.

Homozygous mice on a C57BL/6 congenic background (B6-TRAF1^-/-) have abnormal memory T cell survival and impaired influenza virus CD8 T cell responses. Activated B6-TRAF1^-/- T cells accumulate increased levels of proapoptotic BH3-only family member Bim, particularly the most toxic isoform, Bim_s. The donating investigator reports that B6-TRAF1 mutant mice may be difficult to breed and gain more weight than BALB/c-TRAF1 mutant mice. TRAF1 strains may be useful in studying negative regulation of tumor necrosis factor (TNF) signaling, NF-kB and AP-1 signaling, T cell receptor (TCR)-induced proliferation of T cells, Th2 responses, TRAF1/Bim function in CD8 memory T cell survival, allergic airway diseases and Rheumatoid arthritis, as well as the role of TRAF1 activation in the pathogenesis of lymphomas.

Of note, TRAF1 mutant mice are available on either a BALB/c congenic (Stock No. 008074) or C57BL/6 congenic (Stock No. 008076) background.

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 targeted mutation was generated in the laboratory of Dr. Erdyni Tsitsikov (Immune Disease Institute (formerly CBRI), Boston, Massachusetts). The targeting vector was designed to replace exons 2-5 (beginning at the first coding exon) with a neomycin resistance gene. This construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred with BALB/c females. Heterozygotes were then backcrossed to BALB/cAnNCrl inbred mice for many generations. In 2002, mutant mice were sent to Dr. Gloria Pryhuber (University of Rochester School of Medicine and Dentistry) and rederived using BALB/c inbred mice (most likely BALB/cJ). The resulting mice were made homozygous and then found to be less sensitive to intratracheal treatment of TNF&alpha than reported for the original Traf1-mutant mice from Tsitsikov's lab. Therefore, these mutant mice were subsequently bred to wildtype siblings for approximately 5 generations and then made homozygous. The resulting Traf1-deficient homozygous mice were found to be more sensitive to intratracheal treatment of TNF&alpha (like the original Traf1-mutant mice from Tsitsikov's lab). Homozygous mice were then sent to The Jackson Laboratory. Upon arrival, mice were bred to BALB/cJ inbred mice (Stock No. 000651) for at least one generation to establish the current colony.

Control Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Bryce PJ; Oyoshi MK; Kawamoto S; Oettgen HC; Tsitsikov EN. 2006. TRAF1 regulates Th2 differentiation, allergic inflammation and nuclear localization of the Th2 transcription factor, NIP45. Int Immunol 18(1):101-11PubMed: 16352630 MGI: J:104165
Oyoshi MK; Barthel R; Tsitsikov EN. 2007. TRAF1 regulates recruitment of lymphocytes and, to a lesser extent, neutrophils, myeloid dendritic cells and monocytes to the lung airways following lipopolysaccharide inhalation. Immunology 120(3):303-14PubMed: 17328785 MGI: J:122710
Pryhuber GS; Huyck HL; Roper JM; Cornejo J; O'reilly MA; Pierce RH; Tsitsikov EN. 2005. Acute Tumor Necrosis Factor-{alpha}-Induced Liver Injury in the Absence of Tumor Necrosis Factor Receptor-Associated Factor 1 Gene Expression. Am J Pathol 166(6):1637-45PubMed: 15920149 MGI: J:98818
Sabbagh L; Srokowski CC; Pulle G; Snell LM; Sedgmen BJ; Liu Y; Tsitsikov EN; Watts TH. 2006. A critical role for TNF receptor-associated factor 1 and Bim down-regulation in CD8 memory T cell survival. Proc Natl Acad Sci U S A 103(49):18703-8PubMed: 17116875 MGI: J:118166
Tsitsikov EN; Laouini D; Dunn IF; Sannikova TY; Davidson L; Alt FW; Geha RS. 2001. Traf1 is a negative regulator of tnf signaling. enhanced tnf signaling in traf1-deficient mice. Immunity 15(4):647-57PubMed: 11672546 MGI: J:72327
Zhang B; Wang Z; Li T; Tsitsikov EN; Ding HF. 2007. NF-kappaB2 mutation targets TRAF1 to induce lymphomagenesis. Blood 110(2):743-51PubMed: 17405906 MGI: J:123872

View All References

Genetics

Traf1^tm1Tsi

Allele Symbol: Traf1^tm1Tsi

Allele Name	targeted mutation 1, Erdyni Y Tsitsikov
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	TRAF1^-
Gene Symbol and Name	Traf1, TNF receptor-associated factor 1
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	2
Molecular Note	The gene was disrupted by replacement of exons 2-5 with a neomycin resistance cassette. Homozygous mutant animals did not express protein product as determined by Western blot analysis of stimulated splenocytes using polyclonal antibodies directed against the C-terminus of the protein.
Mutations Made By	Erdyni Tsitsikov, Immune Disease Institute (formerly CBRI)

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Apoptosis Research
- Endogenous Regulators
Cell Biology Research
- Genes Regulating Growth and Proliferation
- Signal Transduction
- Transcriptional Regulation
Cancer Research
- Genes Regulating Growth and Proliferation
- Growth Factors/Receptors/Cytokines
Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis
  - Mutagenesis and Transgenesis: transcriptional activation
- Apoptosis Research
- Cancer Research
  - production of B and T cells, antibodies, and hybridomas
  - production of T cells and hybridoma
  - genes regulating lymphoma development
  - T cell deficiency
- Immunology, Inflammation and Autoimmunity Research
  - T Cell Receptor Deficiency
  - production of B cells, antibodies T cell lines, and hybridomas
  - production of T cell lines and hybridomas
  - T cell deficiency
- Cell Biology Research
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
- Intracellular Signaling Molecules
- Autoimmunity
- Lymphoid Tissue Defects
- Immunodeficiency
  - T cell deficiency
- T Cell Receptor Signaling Defects
Internal/Organ Research
- Lymphoid Tissue Defects
  - T cell deficiency

Mammalian Phenotype Terms by Genotype

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

Genotype: Traf1^tm1Tsi/Traf1^tm1Tsi
involves: 129S4/SvJae * C57BL/6

cellular phenotype

increased T cell proliferation
- Normal - U incorporation of Vbeta8-bearing T cells, and apoptosis of CD4+ and CD8+ populations by annexin V-FITC staining
- increased T cell proliferation persists following stimulation with submitogenic concentrations of anti-CD3 mAb and increasing concentrations of CD28 mAb or of recombinant IL-2
- in culture, mutant splenic T cells show higher proliferation to immobilized anti-CD3 mAb than wild-type T cells; however, no differences in annexin V staining, expression of CD25 (IL-2R-alpha) or intracellular IL-2 protein content are observed
- activated mutant, but not wild-type, T cells respond to TNF by activation of the NF-kappaB and AP-1 signaling pathways
- proliferation of activated mutant T cells to TNF is abrogated by antagonistic mAb to TNF receptor superfamily, member 1b (TNFR2, p75) but not by antagonistic mAb to TNF receptor superfamily, member 1a (TNFR1, p55)
- Normal - however, following injection of staphylococcal enterotoxin B (SEB), homozygotes display normal superantigen-induced clonal expansion and deletion of peripheral Vbeta8-bearing T cells, as determined by changes in lymph node Vbeta8+ and Vbeta6+ subsets, BrdU incorporation of Vbeta8-bearing T cells, and apoptosis of CD4+ and CD8+ populations by annexin V-FITC staining
- following prestimulation with anti-CD3 mAb, activated mutant, but not wild-type, T cells, respond to TNF by proliferation, as determined by [3H]-thymidine incorporation

increased sensitivity to induced cell death
- following subcutaneous injection of a suboptimal TNF dose (1.5 ug/day for 5 days), homozygotes display significantly more skin ulcerations and hemorrhages than wild-type controls, with complete loss of the epidermis and extensive cellular damage in dermis and hypodermis, including vacuolization and disintegration
- homozygotes display increased sensitivity to TNF-induced skin necrosis relative to wild-type controls
- and hypodermis, including vacuolization and disintegration

hematopoietic system phenotype

increased T cell proliferation
- activated mutant, but not wild-type, T cells respond to TNF by activation of the NF-kappaB and AP-1 signaling pathways
- following prestimulation with anti-CD3 mAb, activated mutant, but not wild-type, T cells, respond to TNF by proliferation, as determined by [3H]-thymidine incorporation
- Normal - however, following injection of staphylococcal enterotoxin B (SEB), homozygotes display normal superantigen-induced clonal expansion and deletion of peripheral Vbeta8-bearing T cells, as determined by changes in lymph node Vbeta8+ and Vbeta6+ subsets, BrdU incorporation of Vbeta8-bearing T cells, and apoptosis of CD4+ and CD8+ populations by annexin V-FITC staining
- in culture, mutant splenic T cells show higher proliferation to immobilized anti-CD3 mAb than wild-type T cells; however, no differences in annexin V staining, expression of CD25 (IL-2R-alpha) or intracellular IL-2 protein content are observed
- increased T cell proliferation persists following stimulation with submitogenic concentrations of anti-CD3 mAb and increasing concentrations of CD28 mAb or of recombinant IL-2
- Normal - U incorporation of Vbeta8-bearing T cells, and apoptosis of CD4+ and CD8+ populations by annexin V-FITC staining
- proliferation of activated mutant T cells to TNF is abrogated by antagonistic mAb to TNF receptor superfamily, member 1b (TNFR2, p75) but not by antagonistic mAb to TNF receptor superfamily, member 1a (TNFR1, p55)

increased lymphocyte cell number
- homozygotes show a significant increase of total lymphocyte number in inguinal lymph nodes relative to wild-type controls

immune system phenotype

increased T cell proliferation
- following prestimulation with anti-CD3 mAb, activated mutant, but not wild-type, T cells, respond to TNF by proliferation, as determined by [3H]-thymidine incorporation
- Normal - however, following injection of staphylococcal enterotoxin B (SEB), homozygotes display normal superantigen-induced clonal expansion and deletion of peripheral Vbeta8-bearing T cells, as determined by changes in lymph node Vbeta8+ and Vbeta6+ subsets, BrdU incorporation of Vbeta8-bearing T cells, and apoptosis of CD4+ and CD8+ populations by annexin V-FITC staining
- in culture, mutant splenic T cells show higher proliferation to immobilized anti-CD3 mAb than wild-type T cells; however, no differences in annexin V staining, expression of CD25 (IL-2R-alpha) or intracellular IL-2 protein content are observed
- increased T cell proliferation persists following stimulation with submitogenic concentrations of anti-CD3 mAb and increasing concentrations of CD28 mAb or of recombinant IL-2
- Normal - U incorporation of Vbeta8-bearing T cells, and apoptosis of CD4+ and CD8+ populations by annexin V-FITC staining
- activated mutant, but not wild-type, T cells respond to TNF by activation of the NF-kappaB and AP-1 signaling pathways
- proliferation of activated mutant T cells to TNF is abrogated by antagonistic mAb to TNF receptor superfamily, member 1b (TNFR2, p75) but not by antagonistic mAb to TNF receptor superfamily, member 1a (TNFR1, p55)

abnormal lymph node cell ratio
- Normal - however, the CD4/CD8 ratio remains normal
- homozygotes exhibit an increased T/B cell ratio in inguinal lymph nodes relative to wild-type controls

increased lymphocyte cell number
- homozygotes show a significant increase of total lymphocyte number in inguinal lymph nodes relative to wild-type controls

mammalian phenotype

immune system phenotype
- Normal - homozygotes display normal T and B lymphocyte development, with no differences in thymus or spleen size relative to wild-type controls
- Normal - homozygotes display normal antibody responses to T-dependent antigens (ovalbumin) and type 1 and type 2 T-independent antigens (TNP-LPS and TNP-Ficoll, respectively)
- Normal - in culture, mutant splenic B cells show normal proliferation to anti-IgM and anti-CD40 stimulation as well as normal activation of NF-kappaB and AP-1 following CD40 ligation

References

Bryce PJ; Oyoshi MK; Kawamoto S; Oettgen HC; Tsitsikov EN. 2006. TRAF1 regulates Th2 differentiation, allergic inflammation and nuclear localization of the Th2 transcription factor, NIP45. Int Immunol 18(1):101-11PubMed: 16352630 MGI: J:104165
Oyoshi MK; Barthel R; Tsitsikov EN. 2007. TRAF1 regulates recruitment of lymphocytes and, to a lesser extent, neutrophils, myeloid dendritic cells and monocytes to the lung airways following lipopolysaccharide inhalation. Immunology 120(3):303-14PubMed: 17328785 MGI: J:122710
Pryhuber GS; Huyck HL; Roper JM; Cornejo J; O'reilly MA; Pierce RH; Tsitsikov EN. 2005. Acute Tumor Necrosis Factor-{alpha}-Induced Liver Injury in the Absence of Tumor Necrosis Factor Receptor-Associated Factor 1 Gene Expression. Am J Pathol 166(6):1637-45PubMed: 15920149 MGI: J:98818
Sabbagh L; Srokowski CC; Pulle G; Snell LM; Sedgmen BJ; Liu Y; Tsitsikov EN; Watts TH. 2006. A critical role for TNF receptor-associated factor 1 and Bim down-regulation in CD8 memory T cell survival. Proc Natl Acad Sci U S A 103(49):18703-8PubMed: 17116875 MGI: J:118166
Tsitsikov EN; Laouini D; Dunn IF; Sannikova TY; Davidson L; Alt FW; Geha RS. 2001. Traf1 is a negative regulator of tnf signaling. enhanced tnf signaling in traf1-deficient mice. Immunity 15(4):647-57PubMed: 11672546 MGI: J:72327
Zhang B; Wang Z; Li T; Tsitsikov EN; Ding HF. 2007. NF-kappaB2 mutation targets TRAF1 to induce lymphomagenesis. Blood 110(2):743-51PubMed: 17405906 MGI: J:123872

Additional - Traf1^tm1Tsi related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Traf1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice may be bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the C.129S4-Traf1^tm1Tsi/TsiPryhJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #008074 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

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Genotype

Price

weeks

Cryorecovery - Pricing

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The Jackson Laboratory's Genotype Promise

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:BALB/c-TRAF1, BALB/c TRAF1

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Traf1tm1Tsi

Allele Symbol: Traf1tm1Tsi

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Traf1tm1Tsi/Traf1tm1Tsiinvolves: 129S4/SvJae * C57BL/6

cellular phenotype

hematopoietic system phenotype

immune system phenotype

mammalian phenotype

References

Additional - Traf1tm1Tsi related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Traf1^tm1Tsi

Allele Symbol: Traf1^tm1Tsi

Genotype: Traf1^tm1Tsi/Traf1^tm1Tsi
involves: 129S4/SvJae * C57BL/6

Additional - Traf1^tm1Tsi related