Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Erdyni Tsitsikov,   Immune Disease Institute (formerly CBRI)

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.

Control Information

	Control
	001026 BALB/cByJ	(approximate)
	000651 BALB/cJ	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Traf1^tm1Tsi allele

008076

B6.129S4-Traf1tm1Tsi/J

View Strains carrying   Traf1^tm1Tsi     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Traf1^tm1Tsi/Traf1^tm1Tsi

        involves: 129S4/SvJae * C57BL/6

• immune system phenotype
• increased T cell proliferation (MGI Ref ID J:72327)
  • enhanced proliferation in response to anti-CD3 stimulation, but normal lymphocyte development
• skin/coat/nails phenotype
• abnormal skin physiology (MGI Ref ID J:72327)
  • increased sensitivity of skin to TNF-induced necrosis
• hematopoietic system phenotype
• increased T cell proliferation (MGI Ref ID J:72327)
  • enhanced proliferation in response to anti-CD3 stimulation, but normal lymphocyte development

View Research Applications

Research Applications

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

Apoptosis Research
Endogenous Regulators

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

Cell Biology Research
Genes Regulating Growth and Proliferation
Signal Transduction
Transcriptional Regulation

Immunology and Inflammation Research
Autoimmunity
Growth Factors/Receptors/Cytokines
Immunodeficiency (T cell deficiency)
Intracellular Signaling Molecules
Lymphoid Tissue Defects
T Cell Receptor Signaling Defects

Internal/Organ Research
Lymphoid Tissue Defects (T cell deficiency)

Research Tools
Apoptosis Research
Cancer Research (T cell deficiency)
Cancer Research (genes regulating lymphoma development)
Cancer Research (production of B and T cells, antibodies, and hybridomas)
Cancer Research (production of T cells and hybridoma)
Cell Biology Research
Genetics Research (Mutagenesis and Transgenesis: transcriptional activation)
Immunology and Inflammation Research (T Cell Receptor Deficiency)
Immunology and Inflammation Research (T cell deficiency)
Immunology and Inflammation Research (production of B cells, antibodies T cell lines, and hybridomas)
Immunology and Inflammation Research (production of T cell lines and hybridomas)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Traf1tm1Tsi
Allele Name		targeted mutation 1, Erdyni Y Tsitsikov
Allele Type		Targeted (knock-out)
Common Name(s)		TRAF1-;
Mutation Made By		Erdyni Tsitsikov,   Immune Disease Institute (formerly CBRI)
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Traf1, Tnf receptor-associated factor 1
Chromosome		2
Gene Common Name(s)		4732496E14Rik; EBI6; MGC:10353; RIKEN cDNA 4732496E14 gene;
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. [MGI Ref ID J:72327]

Genotyping

Genotyping Information

Genotyping Protocols

Traf1^tm1Tsi, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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):101-11. [PubMed: 16352630]  [MGI Ref ID 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):303-14. [PubMed: 17328785]  [MGI Ref ID 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):1637-45. [PubMed: 15920149]  [MGI Ref ID 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):18703-8. [PubMed: 17116875]  [MGI Ref ID 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):647-57. [PubMed: 11672546]  [MGI Ref ID J:72327]

Zhang B; Wang Z; Li T; Tsitsikov EN; Ding HF. 2007. NF-kappaB2 mutation targets TRAF1 to induce lymphomagenesis. Blood 110(2):743-51. [PubMed: 17405906]  [MGI Ref ID J:123872]

Additional References

Traf1^tm1Tsi related

Oyoshi MK; Bryce P; Goya S; Pichavant M; Umetsu DT; Oettgen HC; Tsitsikov EN. 2008. TNF receptor-associated factor 1 expressed in resident lung cells is required for the development of allergic lung inflammation. J Immunol 180(3):1878-85. [PubMed: 18209085]  [MGI Ref ID J:131500]

Sabbagh L; Pulle G; Liu Y; Tsitsikov EN; Watts TH. 2008. ERK-dependent Bim modulation downstream of the 4-1BB-TRAF1 signaling axis is a critical mediator of CD8 T cell survival in vivo. J Immunol 180(12):8093-101. [PubMed: 18523273]  [MGI Ref ID J:137236]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice may be bred as homozygotes.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development and On Hold

Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	001026 BALB/cByJ	(approximate)
	000651 BALB/cJ	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.