These tumor necrosis factor null knock-out mice may be useful in studies of susceptibility to parasitic and bacterial infection, endotoxin sensitivity and immune response.
Dr. George Kollias, Biomedical Sciences Research Centre Alexander Fleming
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Tnf | tumor necrosis factor |
Mice homozygous for the Tnftm1Gkl targeted mutation are viable and fertile. Development of both lymph nodes and Peyer's patches is normal, and homozygous mutant mice show no apparent phenotypic abnormalities. Homozygous mice completely lack splenic primary B cell follicles and cannot form organized follicular dendritic cell networks and germinal centers. TNF-deficient mice treated to induce skin carcinogenesis develop significantly less benign and malignant tumors than treated wildtype mice. Nonobese homozygous mutant mice show modest decreases in body weight, epididymal fat depot weight, and percent body fat (statistically significant in males at 28 weeks of age). Further characterization indicates that 28 week old male mutant mice display lower insulin, triglyceride, and leptin levels compared to wildtype controls. Characterization of TNF deficient homozygotes injected with gold-thioglucose (GTG) to induce hyperphagic obesity indicates that the presence of TNF does not affect the degree of obesity. However, fasting plasma glucose and insulin levels, and the insulin response to an oral glucose load were significantly decreased in obese TNF deficient mice compared to obese wildtype controls. These results indicate TNF plays a role in lipid and glucose metabolism but is not sufficient to completely eliminate hyperglycemia and hyperinsulinemia in this induced obesity model.
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. This is the case for the strain above. 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 targeting vector was constructed by replacing with an MC1neopA cassette (Stratagene) the 438-bp Narl-BglII fragment containing 40 bp of the 5' UTR, all the coding region, including the ATG translation initiation codon, of the first exon and part of the first intron of the muTNFa gene. The construct was electroporated into 129S/SvEv-Gpi1c-derived CCE embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice before being intercrossed to produce homozygotes. The mice were then backcrossed to BALB/cByJ for 5 generations (using a speed congenic protocol) before being made homozygous.
Allele Name | targeted mutation 1, George Kollias |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | TNF-; Tnf0; Tnf-alpha-; TNFalpha KO; TNFalpha-; TNFKO |
Gene Symbol and Name | Tnf, tumor necrosis factor |
Gene Synonym(s) | |
Strain of Origin | 129S/SvEv-Gpi1c |
Chromosome | 17 |
Molecular Note | Replacement of 40 bp of the 5' UTR, all the coding region, including the ATG translation initiation codon, of the first exon and part of the first intron with MC1neopA cassette. Northern blot analysis of LPS stimulated macrophages confirmed disruption of Tnf mRNA expression. |
Mutations Made By | Dr. George Kollias, Biomedical Sciences Research Centre Alexander Fleming |
When maintaining a live colony, these mice can be bred as homozygotes.
When using the TNFα- mouse strain in a publication, please cite the originating article(s) and include JAX stock #007082 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Tnf<tm1Gkl> |
Frozen Mouse Embryo | CByJ.129S(B6)-Tnf<tm1Gkl>/J | $2595.00 |
Frozen Mouse Embryo | CByJ.129S(B6)-Tnf<tm1Gkl>/J | $2595.00 |
Frozen Mouse Embryo | CByJ.129S(B6)-Tnf<tm1Gkl>/J | $3373.50 |
Frozen Mouse Embryo | CByJ.129S(B6)-Tnf<tm1Gkl>/J | $3373.50 |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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