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)|
|Gene Symbol and Name||Traf2, TNF receptor-associated factor 2|
|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.
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