Traf2 (TNF receptor-associated factor 2) knock-out mice exhibit a high percentage of perinatal lethality, lymphopenia, high levels of serum TNF and an increased susceptibility to TNF-induced cell death. These mice may be useful for studies of TNF signaling and TNF-induced apoptosis.
Dr. Tak Mak, University Health Network/Un of Toronto
The Traf2 (TNF receptor-associated factor 2) gene belongs to a family of six intracellular signal transducers and is a component of the TNFR1 and TNFR2 complexes that are formed following TNF stimulation. Mice homozygous for this knock-out allele appear normal at birth, but become progressively runted and most die by 10-14 days. Although no developmental or morphological abnormalities are observed, the viability of homozygous embryos decreases after E14.5, the effect is more pronounced when the genetic background contains more alleles from C57BL/6. At death, mice are 20% to 50% the size of normal controls and exhibit decreased muscle mass and fat deposits. In addition, both the thymus and spleen are depleted of lymphocytes. Peripheral blood cells show loss of both T and B lymphocytes and relative granulocytosis. In the absence of Traf2 serum TNF levels are increased and thymocytes and other hematopoietic progenitors become susceptible to TNF-induced cell death. Examination of Traf2-deficient cells reveals a severe reduction in TNF-mediated JNK/SAPK activation, but a mild effect on NF-kappaB activation. These mice may be useful for studies of TNF signaling and TNF-induced apoptosis.
The targeting vector used a neomycin cassette, in reverse orientation, to replace the entire ring finger coding region, which consists of two exons separated by a 1.7 kb intron. The construct was electroporated into 129P2/OlaHsd derived E14K embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were bred to C57BL/6J to achieve germline transmission. The mice were then backcrossed to C57BL/6 for 10 generations. Upon arrival, sperm was cryopreserved. To establish a live colony, an aliquot of frozen sperm is used to fertilize oocytes from C57BL/6J females.
|Allele Name||targeted mutation 1, Tak W Mak|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Tak W Mak; Traf2tm1Mak|
|Gene Symbol and Name||Traf2, TNF receptor-associated factor 2|
|Gene Synonym(s)||AI325259; MGC:45012; expressed sequence AI325259; TRAP; TRAP3; RNF117|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A neomycin resistance cassette replaced a genomic fragment containing the two exons encoding the ring finger domain. Immunoprecipitation and western blot analysis on lysates derived from homozygous mice confirmed that no detecable protein was expressed.|
When maintaining a live colony, heterozygous mice may be bred to wildtype siblings. Most homozygotes die by 10-14 days.
When using the traf2- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #44043 in your Materials and Methods section.
"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.