B6.129S-Tnf^tm1Gkl/Flmg

Status	Available to order
EMMA ID	EM:04790
International strain name	B6.129S-Tnf^tm1Gkl/Flmg
Alternative name	TNFα -/-
Strain type	Targeted Mutant Strains : Knock-out
Allele/Transgene symbol	Tnf^tm1Gkl
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	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

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)

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

MGI phenotypes (gene matching)

increased bone mineral density / MGI
abnormal trabecular bone morphology / MGI
increased leukocyte cell number / MGI
increased neutrophil cell number / MGI
increased cell proliferation / MGI
alopecia / MGI
enlarged liver / MGI
abnormal liver physiology / MGI
abnormal spleen morphology / MGI
enlarged spleen / MGI
abnormal Peyer's patch morphology / MGI
abnormal cerebral cortex morphology / MGI
abnormal spermatogenesis / MGI
abnormal lung morphology / MGI
skin lesions / MGI
increased body length / MGI
increased body weight / MGI
decreased body weight / MGI
increased anxiety-related response / MGI
hypoactivity / MGI
impaired coordination / MGI
increased grooming behavior / MGI
abnormal sleep pattern / MGI
abnormal motor coordination/balance / MGI
abnormal myelopoiesis / MGI
abnormal immune system physiology / MGI
altered susceptibility to infection / MGI
impaired macrophage phagocytosis / MGI
abnormal humoral immune response / MGI
decreased IgG level / MGI
decreased IgA level / MGI
thymus hypoplasia / MGI
autoimmune response / MGI
abnormal inflammatory response / MGI
intestinal inflammation / MGI
lung inflammation / MGI
decreased inflammatory response / MGI
abnormal glucose homeostasis / MGI
premature death / MGI
abnormal lipid homeostasis / MGI
abnormal lymph node B cell domain morphology / MGI
abnormal lymph node primary follicle morphology / MGI
abnormal spleen white pulp morphology / MGI
abnormal spleen marginal zone morphology / MGI
abnormal spleen marginal sinus morphology / MGI
abnormal Peyer's patch follicle morphology / MGI
abnormal Peyer's patch germinal center morphology / MGI
abnormal Peyer's patch T cell area morphology / MGI
decreased susceptibility to bacterial infection / MGI
increased susceptibility to bacterial infection / MGI
increased susceptibility to viral infection / MGI
abnormal T cell physiology / MGI
abnormal macrophage physiology / MGI
decreased immunoglobulin level / MGI
abnormal neutrophil physiology / MGI
increased IgM level / MGI
hepatic steatosis / MGI
decreased circulating triglyceride level / MGI
oligozoospermia / MGI
enhanced wound healing / MGI
decreased circulating insulin level / MGI
abnormal aortic valve morphology / MGI
decreased vertical activity / MGI
abnormal testes secretion / MGI
steatorrhea / MGI
absent Peyer's patches / MGI
increased heart weight / MGI
abnormal joint morphology / MGI
increased liver weight / MGI
arthritis / MGI
abnormal cytokine secretion / MGI
no phenotypic analysis / MGI
decreased coping response / MGI
cardiac fibrosis / MGI
prolonged QT interval / MGI
small intestinal inflammation / MGI
decreased cardiac output / MGI
decreased susceptibility to induced arthritis / MGI
rheumatoid arthritis / MGI
abnormal female reproductive system physiology / MGI
abnormal T cell subpopulation ratio / MGI
abnormal lymphocyte physiology / MGI
abnormal spermiation / MGI
long tibia / MGI
decreased incidence of tumors by chemical induction / MGI
decreased susceptibility to experimental autoimmune encephalomyelitis / MGI
abnormal class switch recombination / MGI
decreased testis weight / MGI
abnormal testis physiology / MGI
skin inflammation / MGI
increased spleen weight / MGI
increased osteoblast cell number / MGI
abnormal CD8-positive, alpha beta T cell morphology / MGI
increased lymphocyte cell number / MGI
increased B cell number / MGI
decreased T cell number / MGI
decreased susceptibility to parasitic infection / MGI
increased susceptibility to parasitic infection / MGI
abnormal cytotoxic T cell physiology / MGI
increased susceptibility to injury / MGI
abnormal mesenteric lymph node morphology / MGI
decreased heart rate / MGI
abnormal fat pad morphology / MGI
decreased susceptibility to autoimmune disorder / MGI
liver/biliary system phenotype / MGI
immune system phenotype / MGI
increased susceptibility to fungal infection / MGI
abnormal food intake / MGI
decreased percent body fat/body weight / MGI
abnormal CD4-positive, alpha-beta T cell physiology / MGI
decreased circulating glucose level / MGI
decreased ventricle muscle contractility / MGI
decreased susceptibility to type IV hypersensitivity reaction / MGI
increased susceptibility to diet-induced obesity / MGI
decreased susceptibility to diet-induced obesity / MGI
abnormal circulating leptin level / MGI
decreased circulating leptin level / MGI
abnormal response to transplant / MGI
increased apoptosis / MGI
decreased apoptosis / MGI
increased body mass index / MGI
aortic valve stenosis / MGI
absent lymph nodes / MGI
increased CD4-positive, alpha beta T cell number / MGI
increased CD8-positive, alpha-beta T cell number / MGI
lymph node hypoplasia / MGI
increased dendritic cell number / MGI
decreased Peyer's patch number / MGI
small Peyer's patches / MGI
absent germinal center B cells / MGI
abnormal follicular dendritic cell physiology / MGI
decreased follicular dendritic cell number / MGI
absent follicular dendritic cells / MGI
absent spleen marginal zone / MGI
abnormal metallophilic macrophage morphology / MGI
abnormal gamma-delta T cell morphology / MGI
abnormal alpha-beta intraepithelial T cell morphology / MGI
abnormal long term spatial reference memory / MGI
absent peripheral lymph nodes / MGI
absent mesenteric lymph nodes / MGI
abnormal spleen B cell follicle morphology / MGI
abnormal spleen primary B follicle morphology / MGI
abnormal spleen follicular dendritic cell network / MGI
absent spleen germinal center / MGI
intermingled spleen red and white pulp / MGI
decreased spleen white pulp amount / MGI
decreased spleen germinal center number / MGI
decreased spleen germinal center size / MGI
decreased IgG1 level / MGI
decreased IgG2a level / MGI
decreased IgG3 level / MGI
absent lymph node germinal center / MGI
increased circulating tumor necrosis factor level / MGI
decreased circulating tumor necrosis factor level / MGI
increased tumor necrosis factor secretion / MGI
decreased tumor necrosis factor secretion / MGI
increased interferon-gamma secretion / MGI
decreased interferon-gamma secretion / MGI
decreased circulating interferon-gamma level / MGI
decreased circulating interleukin-6 level / MGI
decreased circulating interleukin-1 alpha level / MGI
decreased circulating interleukin-1 beta level / MGI
increased interleukin-2 secretion / MGI
abnormal cytokine level / MGI
abnormal chemokine secretion / MGI
decreased susceptibility to endotoxin shock / MGI
increased susceptibility to endotoxin shock / MGI
abnormal lymph node cell ratio / MGI
abnormal vagina weight / MGI
prolonged estrus / MGI
ileum inflammation / MGI
decreased keratinocyte proliferation / MGI
absent inguinal lymph nodes / MGI
absent brachial lymph nodes / MGI
absent axillary lymph nodes / MGI
absent cervical lymph nodes / MGI
absent popliteal lymph nodes / MGI
increased sensitivity to induced morbidity/mortality / MGI
decreased sensitivity to induced morbidity/mortality / MGI
increased susceptibility to bacterial infection induced morbidity/mortality / MGI
increased serotonin level / MGI
abnormal intestine physiology / MGI
abnormal circulating chemokine level / MGI
abnormal T-helper 17 cell physiology / MGI
decreased liver free fatty acids level / MGI
thick aortic valve / MGI
increased CD4-positive, alpha-beta memory T cell number / MGI
decreased macrophage cytokine production / MGI
abnormal aorta bulb morphology / MGI
increased fibroblast proliferation / MGI
increased fibroblast cell migration / MGI
increased cell migration / MGI
abnormal aortic valve flow / MGI
alveolar process atrophy / MGI

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

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Order

Availabilities

Requesting frozen sperm or embryos is generally advisable wherever possible, in order to minimise the shipment of live mice.

Frozen sperm. Delivered in 4 weeks (after paperwork in place). €1740^*
Rederivation of mice from frozen stock, delivery time available upon request . €3880^*

Due to the dynamic nature of our processes strain availability may change at short notice. The local repository manager will advise you in these circumstances.

^* In addition users have to cover all the shipping costs (including the cost for returning dry-shippers, where applicable).

More details on pricing and delivery times

Practical information

Genotyping protocol

Example health report
(Current health report will be provided later)

Material Transfer Agreement (MTA)
Distribution of this strain is subject to a provider MTA. Both signing of the MTA and submission of the online EMMA Mutant Request Form are required before material can be shipped.

EMMA conditions
Legally binding conditions for the transfer

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B6.129S-Tnftm1Gkl/Flmg