Description

Strain Information

Former Names B6;129S6-Tnftm1Gkl/J    (Changed: 03-OCT-07 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N1F8 (20-DEC-06)   Donating Investigator George Kollias,   Hellenic Pasteur Institute

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Tnf^tm1Gkl 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.

Development
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-Gpi1^c-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.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Tnf^tm1Gkl allele

005540	B6.129S-Tnftm1Gkl/J
007082	CByJ.129S(B6)-Tnftm1Gkl/J

View Strains carrying   Tnf^tm1Gkl     (2 strains)

Strains carrying other alleles of Tnf

005108	B6.129P2-Ltb/Tnf/Ltatm1Dvk/J
005112	STOCK Ltb/Tnftm1.1Dvk/J

View Strains carrying other alleles of Tnf     (2 strains)

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tnf^tm1Gkl/Tnf^tm1Gkl

        involves: 129S/SvEv * C57BL/6

• growth/size phenotype
• decreased body weight (MGI Ref ID J:42579)
  • at 28 weeks, mutant animals weigh less
• adipose tissue phenotype
• abnormal fat pad morphology (MGI Ref ID J:42579)
• decreased percent body fat (MGI Ref ID J:42579)
• homeostasis/metabolism phenotype
• abnormal glucose homeostasis (MGI Ref ID J:42579)
• decreased circulating glucose level (MGI Ref ID J:42579)
  • decreased fasting plasma glucose concentrations at 28 weeks of age
• decreased circulating insulin level (MGI Ref ID J:42579)
  • decreased plasma insulin concentrations at 28 weeks of age
• abnormal lipid homeostasis (MGI Ref ID J:42579)
• decreased circulating triglyceride level (MGI Ref ID J:42579)
  • decreased plasma triglyceride concentrations at 28 weeks of age
• decreased circulating leptin level (MGI Ref ID J:42579)
  • decreased plasma leptin concentrations at 28 weeks of age
• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:114740)
  • mutant spleen cells isolated 49 days after myelin oligodendrocyte glycoprotein (MOG) display lack of autoimmune T cell responses (proliferation) to MOG peptide, similar to wild type spleen cells mutant spleen cells isolated 49 days after myelin oligodendrocyte glycoprotein (MOG) display lack of autoimmune T cell responses (proliferation) to MOG peptide, similar to wild-type spleen cells
• abnormal Peyer's patch morphology (MGI Ref ID J:40970)
  • the typical subepithelial dome areas fail to form
• abnormal Peyer's patch follicle morphology (MGI Ref ID J:40970)
  • B cells are present but no organized follicles are seen and organized follicular dendritic cell networks are absent
• decreased Peyer's patch number (MGI Ref ID J:40970)
  • average of 2 - 4 per mouse compared to 6 - 8 in wild-type mice
• abnormal inflammatory response (MGI Ref ID J:114740)
  • when treated with D-gal (a hepatotoxin) at 20 mg/animal and doses of lipopolysaccharide (LPS) up to 100ug/25g body weight, mutants are completely resistant to LPS-induced death, but wild-type mice all die at 100-fold lower LPS doses
• abnormal lymph node B cell domain (MGI Ref ID J:40970)
  • B cell follicles and follicular dendritic cell network formation are impaired in mesenteric and peripheral lymph nodes; however, B cells are present and B and T cell areas are segregated
• abnormal lymphocyte physiology (MGI Ref ID J:114740)
  • after intraperitoneal injection of SRBC, mutants exhibit severely impaired SRBC-specific IgG1 antibody responses
• abnormal macrophage physiology (MGI Ref ID J:114740)
  • LPS-stimulated thioglycollate-elicited peritoneal macrophages (TEPMs) cannot induce thymocyte proliferation, but stimulated TEPMs in wild-type and Tnf homozygotes induce thymocyte proliferation with equal efficiency
• abnormal mesenteric lymph node morphology (MGI Ref ID J:114740)
  • mesenteric lymph nodes (MLN) lack organized B cell follicles but occasionally have GC-like regions that are centered in B cell areas
• abnormal spleen follicular dendritic cell network (MGI Ref ID J:42579)
  • organized follicular dendritic cell networks are absent
• abnormal spleen primary B follicle morphology (MGI Ref ID J:47673)
  • absence of splenic primary B cell follicles
• absent follicular dendritic cells (MGI Ref ID J:40970)
  • organized follicular dendritic cell networks are absent
• absent spleen germinal center (MGI Ref ID J:47673)
  • inability to form organized germinal centers
  • after immunization with sheep red blood cells (SRBCs), mutants fail to form organized germinal centers
• decreased susceptibility to experimental autoimmune encephalomyelitis (MGI Ref ID J:114740)
  • 16 days post-immunization with pertussis toxin, mutants begin to show clinical signs of experimental allergic encephalomyelitis (EAE) which progresses to chronic non-remitting disease compared to wild-type mice which show signs of EAE at 12 days post-injectiona and peak EAE occurs at ~15 days, with gradual remission and results in only a mild deficit
• decreased susceptibility to type IV hypersensitivity reaction (MGI Ref ID J:47673)
  • impaired contact hypersensitivity response
• increased susceptibility to bacterial infection (MGI Ref ID J:47673)
  • susceptibility to death from Listeria monocytogenes infection
  • with challenge at high doses (10000 cfu) of Listeria monocytogenes (LM), mutants show high sensitivity with maximal lethality at 6 days post-infection, compared to wild-type; mutants are highly sensitive when challenged with a physiological dose of LM (100 cfu) compared to wild-type
• hematopoietic system phenotype
• abnormal spleen follicular dendritic cell network (MGI Ref ID J:42579)
  • organized follicular dendritic cell networks are absent
• abnormal spleen primary B follicle morphology (MGI Ref ID J:47673)
  • absence of splenic primary B cell follicles
• absent spleen germinal center (MGI Ref ID J:47673)
  • inability to form organized germinal centers
  • after immunization with sheep red blood cells (SRBCs), mutants fail to form organized germinal centers

Tnf^tm1Gkl/Tnf^tm1Gkl

        either: B6.129-Tnf^tm1Gkl or (involves: 129/Sv * C57BL/6)

• immune system phenotype
• decreased Peyer's patch number (MGI Ref ID J:97783)
  • Peyer's patches are fewer in number
• decreased susceptibility to bacterial infection (MGI Ref ID J:97783)
  • homozygotes are protected from LPS/D-Gal induced shock
• increased leukocyte cell number (MGI Ref ID J:97783)
  • a modest increase in peripheral white cell count is seen compared to wild-type mice
• increased lymphocyte cell number (MGI Ref ID J:97783)
  • lymphocyte numbers are increased compared to Tnf^tm1.2Sned homozygotes
• increased neutrophil cell number (MGI Ref ID J:97783)
  • neutrophil numbers are increased compared to Tnf^tm1.2Sned homozygotes
• increased susceptibility to parasitic infection (MGI Ref ID J:97783)
  • homozygotes show increased sensitivity to systemic and alimentary L. monocytogenes infection
• small Peyer's patches (MGI Ref ID J:97783)
• hematopoietic system phenotype
• increased leukocyte cell number (MGI Ref ID J:97783)
  • a modest increase in peripheral white cell count is seen compared to wild-type mice
• increased lymphocyte cell number (MGI Ref ID J:97783)
  • lymphocyte numbers are increased compared to Tnf^tm1.2Sned homozygotes
• increased neutrophil cell number (MGI Ref ID J:97783)
  • neutrophil numbers are increased compared to Tnf^tm1.2Sned homozygotes

Tnf^tm1Gkl/Tnf^tm1Gkl

        involves: 129S/SvEv * C57BL/6J

• immune system phenotype
• abnormal Peyer's patch morphology (MGI Ref ID J:124642)
  • Peyer's patches have a flattened appearance
• abnormal Peyer's patch follicle morphology (MGI Ref ID J:124642)
  • B cells fail to segregate from T cell areas
• abnormal Peyer's patch T cell area (MGI Ref ID J:124642)
  • T cells fail to segregate from B cells
• abnormal Peyer's patch germinal center morphology (MGI Ref ID J:124642)
  • upon immunization with a T cell dependent antigen, germinal centers fail to develop
• decreased Peyer's patch number (MGI Ref ID J:124642)
  • the mean number of Peyer's patches in mutant mice is 5 compared to 7 in wild-type mice
• abnormal metallophillic macrophage morphology (MGI Ref ID J:124642)
  • there are almost no metallophillic macrophages present in the marginal zone
• abnormal spleen follicular dendritic cell network (MGI Ref ID J:124642)
  • upon immunization with a T cell dependent antigen, there is a no formation of a follicular dendritic cell network
• abnormal spleen marginal sinus morphology (MGI Ref ID J:124642)
  • marginal sinus lining cells expressing mucosal addressin cell adhesion molecules are not present when immunized with a T cell antigen
• abnormal spleen primary B follicle morphology (MGI Ref ID J:124642)
  • B cells fail to form a defined primary follicle instead forming a ring-like structure that is partially mixed with the T cell region
• absent spleen germinal center (MGI Ref ID J:124642)
  • upon immunization with T cell dependent antigen, germinal centers fail to develop
• increased susceptibility to bacterial infection (MGI Ref ID J:124642)
  • 7 days after a sublethal dose of Listeria monocytogenes, no mice survive compared to 60% survival of wild-type mice
• hematopoietic system phenotype
• abnormal metallophillic macrophage morphology (MGI Ref ID J:124642)
  • there are almost no metallophillic macrophages present in the marginal zone
• abnormal spleen follicular dendritic cell network (MGI Ref ID J:124642)
  • upon immunization with a T cell dependent antigen, there is a no formation of a follicular dendritic cell network
• abnormal spleen marginal sinus morphology (MGI Ref ID J:124642)
  • marginal sinus lining cells expressing mucosal addressin cell adhesion molecules are not present when immunized with a T cell antigen
• abnormal spleen primary B follicle morphology (MGI Ref ID J:124642)
  • B cells fail to form a defined primary follicle instead forming a ring-like structure that is partially mixed with the T cell region
• absent spleen germinal center (MGI Ref ID J:124642)
  • upon immunization with T cell dependent antigen, germinal centers fail to develop

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Tnf^tm1Gkl/Tnf^tm1Gkl

        involves: 129S/SvEv

• immune system phenotype
• abnormal chemokine physiology (MGI Ref ID J:95684)
  • induction of MCP-1 was reduced in spleens of mutants infected with Listeria monocytogenes
• decreased circulating tumor necrosis factor level (MGI Ref ID J:95684)
  • serum TNF levels were reduced in mutants injected with LPS and could not be detected on day 2 of Listeria monocytogenes infection
• decreased susceptibility to autoimmune disorder (MGI Ref ID J:95684)
  • increased resistance to liver injury after ConA-induced autoimmune hepatitis, with only infiltrating cells but no liver necrosis detected
• decreased susceptibility to endotoxin shock (MGI Ref ID J:95684)
  • protected from S. aureus enterotoxin B induced toxic shock
• increased susceptibility to bacterial infection (MGI Ref ID J:95684)
  • loss of resistance against Listeria monocytogenes infection
• homeostasis/metabolism phenotype
• decreased circulating tumor necrosis factor level (MGI Ref ID J:95684)
  • serum TNF levels were reduced in mutants injected with LPS and could not be detected on day 2 of Listeria monocytogenes infection

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Tnf^tm1Gkl related

Apoptosis Research
Extracellular Modulators

Cancer Research
Growth Factors/Receptors/Cytokines
Increased Tumor Incidence (Skin Cancers: Resistant)

Cardiovascular Research
Hypotriglyceridemia

Diabetes and Obesity Research
Obesity Without Diabetes (induced)

Endocrine Deficiency Research
Spleen Defects

Hematological Research
Immunological Defects

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines
Immunodeficiency
Inflammation
T Cell Receptor Signaling Defects

Internal/Organ Research
Spleen Defects

Neurobiology Research
Neurodegeneration

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tnftm1Gkl
Allele Name		targeted mutation 1, George Kollias
Allele Type		Targeted (knock-out)
Common Name(s)		TNF-; TNFKO; TNFalpha KO; TNFalpha-; Tnf-alpha-; Tnf0; Tnfa-;
Mutation Made By		George Kollias,   Biomed. Sci. Res. Cntr. "Al. Fleming"
Strain of Origin		129S/SvEv-Gpi1
ES Cell Line Name		CCE/EK.CCE
ES Cell Line Strain		129S/SvEv-Gpi1
Gene Symbol and Name		Tnf, tumor necrosis factor
Chromosome		17
Gene Common Name(s)		DIF; MGC124630; RATTNF; TNF alpha; TNF-alpha; TNFA; TNFSF2; TNFalpha; Tnfa; Tnfsf1a; tumor necrosis factor, alpha; tumor necrosis factor-alpha;
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 ofTnf mRNA expression. [MGI Ref ID J:47673]

Genotyping

Genotyping Information

Genotyping Protocols

Tnf^tm1Gkl, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Pasparakis M; Alexopoulou L; Episkopou V; Kollias G. 1996. 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 [see comments] J Exp Med 184(4):1397-411. [PubMed: 8879212]  [MGI Ref ID J:47673]

Additional References

Alexopoulou L; Pasparakis M; Kollias G. 1997. A murine transmembrane tumor necrosis factor (TNF) transgene induces arthritis by cooperative p55/p75 TNF receptor signaling. Eur J Immunol 27(10):2588-92. [PubMed: 9368614]  [MGI Ref ID J:43603]

Bitsaktsis C; Huntington J; Winslow G. 2004. Production of IFN-gamma by CD4 T cells is essential for resolving ehrlichia infection. J Immunol 172(11):6894-901. [PubMed: 15153508]  [MGI Ref ID J:90518]

Kassiotis G; Bauer J; Akassoglou K; Lassmann H; Kollias G; Probert L. 1999. A tumor necrosis factor-induced model of human primary demyelinating diseases develops in immunodeficient mice. Eur J Immunol 29(3):912-7. [PubMed: 10092095]  [MGI Ref ID J:53471]

Kassiotis G; Pasparakis M; Kollias G; Probert L. 1999. TNF accelerates the onset but does not alter the incidence and severity of myelin basic protein-induced experimental autoimmune encephalomyelitis. Eur J Immunol 29(3):774-80. [PubMed: 10092079]  [MGI Ref ID J:53472]

Moore RJ; Owens DM; Stamp G; Arnott C; Burke F; East N; Holdsworth H; Turner L; Rollins B; Pasparakis M; Kollias G; Balkwill F. 1999. Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat Med 5(7):828-831. [PubMed: 10395330]  [MGI Ref ID J:56068]

Neurath MF; Fuss I; Pasparakis M; Alexopoulou L; Haralambous S ; Meyer zum Buschenfelde KH ; Strober W ; Kollias G. 1997. Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice. Eur J Immunol 27(7):1743-50. [PubMed: 9247586]  [MGI Ref ID J:41489]

Ventre J; Doebber T; Wu M; MacNaul K; Stevens K; Pasparakis M ; Kollias G ; Moller DE. 1997. Targeted disruption of the tumor necrosis factor-alpha gene: metabolic consequences in obese and nonobese mice. Diabetes 46(9):1526-31. [PubMed: 9287059]  [MGI Ref ID J:42579]

Tnf^tm1Gkl related

Abe K; Yarovinsky FO; Murakami T; Shakhov AN; Tumanov AV; Ito D; Drutskaya LN; Pfeffer K; Kuprash DV; Komschlies KL; Nedospasov SA. 2003. Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo. Blood 101(4):1477-83. [PubMed: 12560241]  [MGI Ref ID J:115537]

Acharyya S; Villalta SA; Bakkar N; Bupha-Intr T; Janssen PM; Carathers M; Li ZW; Beg AA; Ghosh S; Sahenk Z; Weinstein M; Gardner KL; Rafael-Fortney JA; Karin M; Tidball JG; Baldwin AS; Guttridge DC. 2007. Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. J Clin Invest 117(4):889-901. [PubMed: 17380205]  [MGI Ref ID J:121279]

Akassoglou K; Bauer J; Kassiotis G; Pasparakis M; Lassmann H; Kollias G; Probert L. 1998. Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy. Am J Pathol 153(3):801-13. [PubMed: 9736029]  [MGI Ref ID J:106592]

Akassoglou K; Douni E; Bauer J; Lassmann H; Kollias G; Probert L. 2003. Exclusive tumor necrosis factor (TNF) signaling by the p75TNF receptor triggers inflammatory ischemia in the CNS of transgenic mice. Proc Natl Acad Sci U S A 100(2):709-14. [PubMed: 12522266]  [MGI Ref ID J:135049]

Alexopoulou L; Kranidioti K; Xanthoulea S; Denis M; Kotanidou A; Douni E; Blackshear PJ; Kontoyiannis DL; Kollias G. 2006. Transmembrane TNF protects mutant mice against intracellular bacterial infections, chronic inflammation and autoimmunity. Eur J Immunol 36(10):2768-80. [PubMed: 16983719]  [MGI Ref ID J:114740]

Alexopoulou L; Pasparakis M; Kollias G. 1997. A murine transmembrane tumor necrosis factor (TNF) transgene induces arthritis by cooperative p55/p75 TNF receptor signaling. Eur J Immunol 27(10):2588-92. [PubMed: 9368614]  [MGI Ref ID J:43603]

Anderson AL; Sporici R; Lambris J; Larosa D; Levinson AI. 2006. Pathogenesis of B-cell superantigen-induced immune complex-mediated inflammation. Infect Immun 74(2):1196-203. [PubMed: 16428769]  [MGI Ref ID J:104987]

Andoh M; Zhang G; Russell-Lodrigue KE; Shive HR; Weeks BR; Samuel JE. 2007. T Cells Are Essential for Bacterial Clearance, and Gamma Interferon, Tumor Necrosis Factor Alpha, and B Cells Are Crucial for Disease Development in Coxiella burnetii Infection in Mice. Infect Immun 75(7):3245-55. [PubMed: 17438029]  [MGI Ref ID J:122426]

Andrade RM; Wessendarp M; Portillo JA; Yang JQ; Gomez FJ; Durbin JE; Bishop GA; Subauste CS. 2005. TNF receptor-associated factor 6-dependent CD40 signaling primes macrophages to acquire antimicrobial activity in response to TNF-alpha. J Immunol 175(9):6014-21. [PubMed: 16237096]  [MGI Ref ID J:119350]

Arnett HA; Mason J; Marino M; Suzuki K; Matsushima GK; Ting JP. 2001. TNFalpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat Neurosci 4(11):1116-22. [PubMed: 11600888]  [MGI Ref ID J:72695]

Arsenijevic D; Clavel S; Sanchis D; Plamondon J; Huang Q; Ricquier D; Rouger L; Richard D. 2007. Induction of Ucp2 expression in brain phagocytes and neurons following murine toxoplasmosis: an essential role of IFN-gamma and an association with negative energy balance. J Neuroimmunol 186(1-2):121-32. [PubMed: 17467814]  [MGI Ref ID J:124552]

Ashkar AA; Di Santo JP; Croy BA. 2000. Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy [see comments] J Exp Med 192(2):259-70. [PubMed: 10899912]  [MGI Ref ID J:63645]

Barber EM; Fazzari M; Pollard JW. 2005. Th1 cytokines are essential for placental immunity to Listeria monocytogenes. Infect Immun 73(10):6322-31. [PubMed: 16177303]  [MGI Ref ID J:104232]

Barker V; Middleton G; Davey F; Davies AM. 2001. TNFalpha contributes to the death of NGF-dependent neurons during development. Nat Neurosci 4(12):1194-8. [PubMed: 11685224]  [MGI Ref ID J:109370]

Baxevanis CN; Voutsas IF; Tsitsilonis OE; Tsiatas ML; Gritzapis AD; Papamichail M. 2000. Compromised anti-tumor responses in tumor necrosis factor-alpha knockout mice. Eur J Immunol 30(7):1957-66. [PubMed: 10940885]  [MGI Ref ID J:63509]

Biedermann T; Kneilling M; Mailhammer R; Maier K; Sander CA; Kollias G; Kunkel SL; Hultner L; Rocken M. 2000. Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2 J Exp Med 192(10):1441-52. [PubMed: 11085746]  [MGI Ref ID J:65843]

Binstadt BA; Patel PR; Alencar H; Nigrovic PA; Lee DM; Mahmood U; Weissleder R; Mathis D; Benoist C. 2006. Particularities of the vasculature can promote the organ specificity of autoimmune attack. Nat Immunol 7(3):284-92. [PubMed: 16444258]  [MGI Ref ID J:112604]

Bitsaktsis C; Huntington J; Winslow G. 2004. Production of IFN-gamma by CD4 T cells is essential for resolving ehrlichia infection. J Immunol 172(11):6894-901. [PubMed: 15153508]  [MGI Ref ID J:90518]

Bitsaktsis C; Nandi B; Racine R; MacNamara KC; Winslow G. 2007. T-Cell-independent humoral immunity is sufficient for protection against fatal intracellular ehrlichia infection. Infect Immun 75(10):4933-41. [PubMed: 17664264]  [MGI Ref ID J:125283]

Boesten LS; Zadelaar AS; van Nieuwkoop A; Gijbels MJ; de Winther MP; Havekes LM; van Vlijmen BJ. 2005. Tumor necrosis factor-alpha promotes atherosclerotic lesion progression in APOE*3-Leiden transgenic mice. Cardiovasc Res 66(1):179-85. [PubMed: 15769461]  [MGI Ref ID J:109170]

Boone DL; Turer EE; Lee EG; Ahmad RC; Wheeler MT; Tsui C; Hurley P; Chien M; Chai S; Hitotsumatsu O; McNally E; Pickart C; Ma A. 2004. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat Immunol 5(10):1052-60. [PubMed: 15334086]  [MGI Ref ID J:92694]

Brandl K; Plitas G; Schnabl B; DeMatteo RP; Pamer EG. 2007. MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. J Exp Med 204(8):1891-900. [PubMed: 17635956]  [MGI Ref ID J:125955]

Branen L; Hovgaard L; Nitulescu M; Bengtsson E; Nilsson J; Jovinge S. 2004. Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 24(11):2137-42. [PubMed: 15345516]  [MGI Ref ID J:103699]

Brehm MA; Daniels KA; Welsh RM. 2005. Rapid production of TNF-alpha following TCR engagement of naive CD8 T cells. J Immunol 175(8):5043-9. [PubMed: 16210607]  [MGI Ref ID J:119124]

Buhtoiarov IN; Lum HD; Berke G; Sondel PM; Rakhmilevich AL. 2006. Synergistic activation of macrophages via CD40 and TLR9 results in T cell independent antitumor effects. J Immunol 176(1):309-18. [PubMed: 16365423]  [MGI Ref ID J:126263]

Calzascia T; Pellegrini M; Hall H; Sabbagh L; Ono N; Elford AR; Mak TW; Ohashi PS. 2007. TNF-alpha is critical for antitumor but not antiviral T cell immunity in mice. J Clin Invest 117(12):3833-45. [PubMed: 17992258]  [MGI Ref ID J:130779]

Campana WM; Li X; Dragojlovic N; Janes J; Gaultier A; Gonias SL. 2006. The low-density lipoprotein receptor-related protein is a pro-survival receptor in Schwann cells: possible implications in peripheral nerve injury. J Neurosci 26(43):11197-207. [PubMed: 17065459]  [MGI Ref ID J:114965]

Csiszar A; Smith KE; Koller A; Kaley G; Edwards JG; Ungvari Z. 2005. Regulation of bone morphogenetic protein-2 expression in endothelial cells: role of nuclear factor-kappaB activation by tumor necrosis factor-alpha, H2O2, and high intravascular pressure. Circulation 111(18):2364-72. [PubMed: 15851600]  [MGI Ref ID J:111595]

Cusson N; Oikemus S; Kilpatrick ED; Cunningham L; Kelliher M. 2002. The death domain kinase RIP protects thymocytes from tumor necrosis factor receptor type 2-induced cell death. J Exp Med 196(1):15-26. [PubMed: 12093867]  [MGI Ref ID J:120699]

Dajani R; Sanlioglu S; Zhang Y; Li Q; Monick MM; Lazartigues E; Eggleston T; Davisson RL; Hunninghake GW; Engelhardt JF. 2007. Pleiotropic functions of TNF-alpha determine distinct IKKbeta-dependent hepatocellular fates in response to LPS. Am J Physiol Gastrointest Liver Physiol 292(1):G242-52. [PubMed: 16935850]  [MGI Ref ID J:120596]

Dawn B; Guo Y; Rezazadeh A; Wang OL; Stein AB; Hunt G; Varma J; Xuan YT; Wu WJ; Tan W; Zhu X; Bolli R. 2004. Tumor necrosis factor-alpha does not modulate ischemia/reperfusion injury in naive myocardium but is essential for the development of late preconditioning. J Mol Cell Cardiol 37(1):51-61. [PubMed: 15242735]  [MGI Ref ID J:132469]

Dokun AO; Chu DT; Yang L; Bendelac AS; Yokoyama WM. 2001. Analysis of in situ NK cell responses during viral infection. J Immunol 167(9):5286-93. [PubMed: 11673544]  [MGI Ref ID J:72673]

Domercq M; Brambilla L; Pilati E; Marchaland J; Volterra A; Bezzi P. 2006. P2Y1 receptor-evoked glutamate exocytosis from astrocytes: control by tumor necrosis factor-alpha and prostaglandins. J Biol Chem 281(41):30684-96. [PubMed: 16882655]  [MGI Ref ID J:117295]

Douni E; Kollias G. 1998. A critical role of the p75 tumor necrosis factor receptor (p75TNF-R) in organ inflammation independent of TNF, lymphotoxin alpha, or the p55TNF-R. J Exp Med 188(7):1343-52. [PubMed: 9763613]  [MGI Ref ID J:114744]

Dumitru CD; Ceci JD; Tsatsanis C; Kontoyiannis D; Stamatakis K; Lin JH; Patriotis C; Jenkins NA; Copeland NG; Kollias G; Tsichlis PN. 2000. TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell 103(7):1071-83. [PubMed: 11163183]  [MGI Ref ID J:66503]

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Ueki Y; Lin CY; Senoo M; Ebihara T; Agata N; Onji M; Saheki Y; Kawai T; Mukherjee PM; Reichenberger E; Olsen BR. 2007. Increased myeloid cell responses to M-CSF and RANKL cause bone loss and inflammation in SH3BP2 'cherubism' mice. Cell 128(1):71-83. [PubMed: 17218256]  [MGI Ref ID J:117880]

Vazquez-Torres A; Fantuzzi G; Edwards CK rd; Dinarello CA; Fang FC. 2001. Defective localization of the NADPH phagocyte oxidase to Salmonella-containing phagosomes in tumor necrosis factor p55 receptor-deficient macrophages. Proc Natl Acad Sci U S A 98(5):2561-5. [PubMed: 11226278]  [MGI Ref ID J:126397]

Ventre J; Doebber T; Wu M; MacNaul K; Stevens K; Pasparakis M ; Kollias G ; Moller DE. 1997. Targeted disruption of the tumor necrosis factor-alpha gene: metabolic consequences in obese and nonobese mice. Diabetes 46(9):1526-31. [PubMed: 9287059]  [MGI Ref ID J:42579]

Vila-del Sol V; Diaz-Munoz MD; Fresno M. 2007. Requirement of tumor necrosis factor alpha and nuclear factor-kappaB in the induction by IFN-gamma of inducible nitric oxide synthase in macrophages. J Leukoc Biol 81(1):272-83. [PubMed: 17035338]  [MGI Ref ID J:117247]

Vila-del Sol V; Fresno M. 2005. Involvement of TNF and NF-kappa B in the transcriptional control of cyclooxygenase-2 expression by IFN-gamma in macrophages. J Immunol 174(5):2825-33. [PubMed: 15728492]  [MGI Ref ID J:97728]

Wald O; Weiss ID; Wald H; Shoham H; Bar-Shavit Y; Beider K; Galun E; Weiss L; Flaishon L; Shachar I; Nagler A; Lu B; Gerard C; Gao JL; Mishani E; Farber J; Peled A. 2006. IFN-gamma acts on T cells to induce NK cell mobilization and accumulation in target organs. J Immunol 176(8):4716-29. [PubMed: 16585565]  [MGI Ref ID J:131189]

Wang Y; Wang J; Sun Y; Wu Q; Fu YX. 2001. Complementary effects of TNF and lymphotoxin on the formation of germinal center and follicular dendritic cells J Immunol 166(1):330-7. [PubMed: 11123309]  [MGI Ref ID J:66397]

Weller K; Foitzik K; Paus R; Syska W; Maurer M. 2006. Mast cells are required for normal healing of skin wounds in mice. FASEB J 20(13):2366-8. [PubMed: 16966487]  [MGI Ref ID J:129739]

Wheeler DL; Martin KE; Ness KJ; Li Y; Dreckschmidt NE; Wartman M; Ananthaswamy HN; Mitchell DL; Verma AK. 2004. Protein kinase C epsilon is an endogenous photosensitizer that enhances ultraviolet radiation-induced cutaneous damage and development of squamous cell carcinomas. Cancer Res 64(21):7756-65. [PubMed: 15520180]  [MGI Ref ID J:93804]

Wright HV; Bailey D; Kashyap M; Kepley CL; Drutskaya MS; Nedospasov SA; Ryan JJ. 2006. IL-3-mediated TNF production is necessary for mast cell development. J Immunol 176(4):2114-21. [PubMed: 16455967]  [MGI Ref ID J:129126]

Wu Q; Wang Y; Wang J; Hedgeman EO; Browning JL; Fu YX. 1999. The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissues. J Exp Med 190(5):629-38. [PubMed: 10477548]  [MGI Ref ID J:110887]

Wuthrich M; Filutowicz HI; Warner T; Klein BS. 2002. Requisite elements in vaccine immunity to Blastomyces dermatitidis: plasticity uncovers vaccine potential in immune-deficient hosts. J Immunol 169(12):6969-76. [PubMed: 12471131]  [MGI Ref ID J:118419]

Xanthoulea S; Pasparakis M; Kousteni S; Brakebusch C; Wallach D; Bauer J; Lassmann H; Kollias G. 2004. Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases. J Exp Med 200(3):367-76. [PubMed: 15289505]  [MGI Ref ID J:92470]

Xu L; Yoon H; Zhao MQ; Liu J; Ramana CV; Enelow RI. 2004. Cutting edge: pulmonary immunopathology mediated by antigen-specific expression of TNF-alpha by antiviral CD8+ T cells. J Immunol 173(2):721-5. [PubMed: 15240656]  [MGI Ref ID J:91920]

Yamoah K; Brebene A; Baliram R; Inagaki K; Dolios G; Arabi A; Majeed R; Amano H; Wang R; Yanagisawa R; Abe E. 2008. High-Mobility Group Box Proteins Modulate Tumor Necrosis Factor-{alpha} Expression in Osteoclastogenesis via a Novel Deoxyribonucleic Acid Sequence. Mol Endocrinol 22(5):1141-53. [PubMed: 18218727]  [MGI Ref ID J:134080]

Yi AK; Yoon H; Park JE; Kim BS; Kim HJ; Martinez-Hernandez A. 2006. CpG DNA-mediated induction of acute liver injury in D-galactosamine-sensitized mice: the mitochondrial apoptotic pathway-dependent death of hepatocytes. J Biol Chem 281(21):15001-12. [PubMed: 16554296]  [MGI Ref ID J:113473]

Zganiacz A; Santosuosso M; Wang J; Yang T; Chen L; Anzulovic M; Alexander S; Gicquel B; Wan Y; Bramson J; Inman M; Xing Z. 2004. TNF-alpha is a critical negative regulator of type 1 immune activation during intracellular bacterial infection. J Clin Invest 113(3):401-13. [PubMed: 14755337]  [MGI Ref ID J:87611]

Zhang B; Maris CH; Foell J; Whitmire J; Niu L; Song J; Kwon BS; Vella AT; Ahmed R; Jacob J; Mittler RS. 2007. Immune suppression or enhancement by CD137 T cell costimulation during acute viral infection is time dependent. J Clin Invest 117(10):3029-41. [PubMed: 17853940]  [MGI Ref ID J:127406]

Zhao C; Ling Z; Newman MB; Bhatia A; Carvey PM. 2007. TNF-alpha knockout and minocycline treatment attenuates blood-brain barrier leakage in MPTP-treated mice. Neurobiol Dis 26(1):36-46. [PubMed: 17234424]  [MGI Ref ID J:119001]

Zimmerman MA; Selzman CH; Reznikov LL; Miller SA; Raeburn CD; Emmick J; Meng X; Harken AH. 2002. Lack of TNF-alpha attenuates intimal hyperplasia after mouse carotid artery injury Am J Physiol Regul Integr Comp Physiol 283(2):R505-12. [PubMed: 12121864]  [MGI Ref ID J:113512]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX30

Colony Maintenance

Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply	Level 4. Up to 10 mice. Larger quantities or custom orders arranged upon request. Expected delivery up to one to three months.
Supply Notes	Shipped at a specific age in weeks. Mice at a precise age in days, littermates and retired breeders are also available. Strains that must be genotyped are not available until five to seven weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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.

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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.