C.129S4-Traf1^tm1Tsi/TsiPryhJ

Stock number: 008074
Strain synonyms: BALB/c-TRAF1, BALB/c TRAF1
Research areas: Apoptosis Research, Cancer Research, Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

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.

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.

Allele

Symbol: Traf1^tm1Tsi
Name: targeted mutation 1, Erdyni Y Tsitsikov
MGI accession ID: MGI:2386957
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Traf1
Marker name: TNF receptor-associated factor 1
Chromosome: 2
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.