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.
Gloria Pryhuber, University of Rochester
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, Bims. 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.
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.
|Allele Name||targeted mutation 1, Erdyni Y Tsitsikov|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Traf1tm1Tsi; targeted mutation 1, Erdyni Y Tsitsikov|
|Gene Symbol and Name||Traf1, TNF receptor-associated factor 1|
|Gene Synonym(s)||4732496E14Rik; RIKEN cDNA 4732496E14 gene; EBI6; MGC:10353; 4732496E14Rik|
|Strain of Origin||129S4/SvJae|
|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)
When maintaining a live colony, these mice may be bred as homozygotes.
When using the C.129S4-Traf1tm1Tsi/TsiPryhJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #008074 in your Materials and Methods section.
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (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. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, 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 JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES 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 JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or SERVICES by JACKSON.