- abnormal spermatogenesis / MGI
- oligozoospermia / MGI
- abnormal testes secretion / MGI
- abnormal spermiation / MGI
- decreased testis weight / MGI
- abnormal testis physiology / MGI
- decreased incidence of tumors by chemical induction / MGI
- increased susceptibility to bacterial infection / MGI
- decreased susceptibility to autoimmune disorder / MGI
- decreased circulating tumor necrosis factor level / MGI
- abnormal chemokine secretion / MGI
- decreased susceptibility to endotoxin shock / MGI
- increased bone mineral density / MGI
- abnormal trabecular bone morphology / MGI
- abnormal Peyer's patch morphology / MGI
- decreased body weight / MGI
- abnormal inflammatory response / MGI
- decreased inflammatory response / MGI
- abnormal glucose homeostasis / MGI
- abnormal lipid homeostasis / MGI
- abnormal lymph node B cell domain morphology / MGI
- abnormal Peyer's patch follicle morphology / MGI
- abnormal macrophage physiology / MGI
- decreased circulating triglyceride level / MGI
- decreased circulating insulin level / MGI
- abnormal lymphocyte physiology / MGI
- decreased susceptibility to experimental autoimmune encephalomyelitis / MGI
- increased osteoblast cell number / MGI
- abnormal mesenteric lymph node morphology / MGI
- abnormal fat pad morphology / MGI
- immune system phenotype / MGI
- decreased percent body fat/body weight / MGI
- decreased circulating glucose level / MGI
- decreased susceptibility to type IV hypersensitivity reaction / MGI
- decreased circulating leptin level / MGI
- decreased Peyer's patch number / MGI
- absent follicular dendritic cells / MGI
- abnormal spleen primary B follicle morphology / MGI
- abnormal spleen follicular dendritic cell network / MGI
- absent spleen germinal center / MGI
- decreased keratinocyte proliferation / MGI
- alveolar process atrophy / MGI
- abnormal spleen marginal sinus morphology / MGI
- abnormal Peyer's patch germinal center morphology / MGI
- abnormal Peyer's patch T cell area morphology / MGI
- abnormal metallophilic macrophage morphology / MGI
- increased leukocyte cell number / MGI
- increased neutrophil cell number / MGI
- decreased susceptibility to bacterial infection / MGI
- increased lymphocyte cell number / MGI
- increased susceptibility to parasitic infection / MGI
- small Peyer's patches / MGI
- rheumatoid arthritis / MGI
- increased circulating tumor necrosis factor level / MGI
- increased tumor necrosis factor secretion / MGI
- increased susceptibility to endotoxin shock / MGI
B6.129S-Tnftm1Gkl/Flmg
Status | Available to order |
EMMA ID | EM:04790 |
International strain name | B6.129S-Tnftm1Gkl/Flmg |
Alternative name | TNFα -/- |
Strain type | Targeted Mutant Strains : Knock-out |
Allele/Transgene symbol | Tnftm1Gkl, |
Gene/Transgene symbol | Tnf |
Information from provider
Provider | George Kollias |
Provider affiliation | B.S.R.C. |
Genetic information | The genomic locus containing the genes for TNFalpha and LTalpha was isolated from a 129/Sv mouse genomic library in FIX(TM)II (Stratagene Inc., La Jolla, CA). The targeting vector was constructed by replacing with an MClneopA cassette (Stratagene) the 438-bp NarI-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 neo cassette was flanked by 4.5 and 1.2 kb of homologous sequences, respectively. A thymidine kinase gene under the control of the MC1 promoter was inserted at the 5' end of the targeting vector for negative selection against random integrations. The targeting vector was linearized and electroporated into CCE embryonic stem cells. |
Phenotypic information | TNFa knock-out mice completely lack splenic primary B cell follicles and cannot form organized follicular dendritic cell (FDC) networks and germinal centers. TNFa knock-out mice have deregulated humoral immune responses. In the absence of TNF, mice readily succumb to L. monocytogenes infections and show reduced contact hypersensitivity responses. Furthermore, TNF knock-out mice are resistant to the systemic toxicity of lipopolysaccharide (LPS) upon D-galactosamine sensitization, yet they remain sensitive to high doses of LPS alone. TNFa deficient mice provide useful information for understanding the biological consequences of a long term blockade of TNF functioning, as a means of treating chronic inflammatory and autoimmune pathology in human patients. TNFa knock-out mice should also provide an important model for further analysis of B cell follicles and FDCs function in peripheral B cell homing, survival, and differentiation. |
References |
|
Information from EMMA
Archiving centre | B.S.R.C. Alexander Fleming, Vari, Greece |
Disease and phenotype information
MGI allele-associated human disease models
MGI phenotypes (allele matching)
Literature references
- Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response.;Pasparakis M, Alexopoulou L, Episkopou V, Kollias G, ;1996;The Journal of experimental medicine;184;1397-411; 8879212
- Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies.;Kontoyiannis D, Pasparakis M, Pizarro T T, Cominelli F, Kollias G, ;1999;Immunity;10;387-98; 10204494
INFRAFRONTIER® and European Mouse Mutant Archive - EMMA® are registered trademarks at the European Union Intellectual Property Office (EUIPO).