Strain Name:

B6;129S2-Il6tm1Kopf/J

Stock Number:

002254

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Availability:

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These interleukin 6 (IL6) knock-out mutant mice show defects in responses to various viruses and in inflammatory responses to tissue damage or infection.

Description

Strain Information

Former Names B6;129S6-Il6tm1Kopf    (Changed: 15-DEC-04 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHomozygote x Homozygote         (Female x Male)   01-MAR-06
Specieslaboratory mouse
GenerationF?+40 (05-JAN-09)
Generation Definitions
 
Donating InvestigatorDr. Manfred Kopf,   ETH Zurich

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the targeted mutation are viable and fertile. No gene product (mRNA) is detected by RT-PCR analysis of lipopolysaccharide (LPS) challenged macrophages. Bioassay and enzyme-linked immunosorbent assay (ELISA) analysis of serum from LPS-challenged homozygotes reveals no detectable protein activity. These interleukin 6 (IL6) mutant mice show defects in responses to various viruses and in inflammatory responses to tissue damage or infection.

Of note, IL6-mutant mice may be available on different genetic backgrounds including mixed B6;129S2 (Stock No. 002254), C57BL/6J (Stock No. 002650), and BALB/cByJ (Stock No. 007078).

Development
The interleukin 6 targeted mutation was created by Manfred Kopf and Georges Kohler (Max Planck Institut Fur Immunbiologie, Freiburg Germany). A targeting vector was designed to place a neomycin resistance cassette into the first coding exon (exon 2) of the targeted gene. This construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Heterozygotes were intercrossed to generate homozygotes.

Control Information

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

Related Strains

Strains carrying   Il6tm1Kopf allele
002650   B6.129S2-Il6tm1Kopf/J
021873   BXSB.129S2(B6)-Il6tm1Kopf/DcrJ
007078   CByJ.129S2(B6)-Il6tm1Kopf/J
View Strains carrying   Il6tm1Kopf     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Arteriovenous Malformations of the Brain   (IL6)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM   (IL6)
Inflammatory Bowel Disease 1; IBD1   (IL6)
Kaposi Sarcoma, Susceptibility to   (IL6)
Rheumatoid Arthritis, Systemic Juvenile   (IL6)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Il6tm1Kopf/Il6tm1Kopf

        involves: 129S2/SvPas * C57BL/6
  • growth/size/body phenotype
  • decreased body weight
    • lower body weight at 4 months of age is due largely to lower fat mass   (MGI Ref ID J:105633)
  • obese
    • obesity develops by 8 months of age   (MGI Ref ID J:105633)
  • immune system phenotype
  • abnormal T cell differentiation
    • thymocytes are consistently reduced by 20-40%   (MGI Ref ID J:17360)
  • abnormal acute phase protein level
    • 100-fold reduction in SAA production by the liver in response to turpentine injection or listeria infection   (MGI Ref ID J:17360)
  • abnormal microglial cell morphology
    • modest increase in microglial density after haloperidol treatment relative to the increase seen in controls   (MGI Ref ID J:79142)
  • decreased T cell number
    • T cells are reduced in the periphery by 20-40%   (MGI Ref ID J:17360)
  • decreased cytotoxic T cell cytolysis
    • cytolytic activity of CD8 T cells to vaccinia virus infected cells is reduced 3-10 fold   (MGI Ref ID J:17360)
  • increased susceptibility to bacterial infection
    • 10 to 100 fold increase in bacterial titers in the liver and spleen of mice infected with Listeria   (MGI Ref ID J:17360)
  • increased susceptibility to induced colitis
    • severe erosion of the intestinal epithelium from exposure to 3.5% dextran sodium sulfate   (MGI Ref ID J:79073)
  • increased susceptibility to viral infection
    • viral titers are 10-1000 fold higher in the ovaries and lungs of vaccinia virus infected mice   (MGI Ref ID J:17360)
  • hematopoietic system phenotype
  • abnormal T cell differentiation
    • thymocytes are consistently reduced by 20-40%   (MGI Ref ID J:17360)
  • abnormal microglial cell morphology
    • modest increase in microglial density after haloperidol treatment relative to the increase seen in controls   (MGI Ref ID J:79142)
  • decreased T cell number
    • T cells are reduced in the periphery by 20-40%   (MGI Ref ID J:17360)
  • decreased cytotoxic T cell cytolysis
    • cytolytic activity of CD8 T cells to vaccinia virus infected cells is reduced 3-10 fold   (MGI Ref ID J:17360)
  • cardiovascular system phenotype
  • abnormal capillary morphology
    • fewer capillaries in the heart   (MGI Ref ID J:150895)
  • abnormal cardiovascular system physiology
    • increased cell proliferation and apoptosis in 5 day old hearts   (MGI Ref ID J:150895)
    • proliferation at 5 days primarily by non myocytes   (MGI Ref ID J:150895)
    • apoptosis at 5 days primarily of myocytes   (MGI Ref ID J:150895)
    • decreased cardiac muscle contractility
      • both fractional shortening and ejection fraction are decreased in adults and at 5 and 15 days of age   (MGI Ref ID J:150895)
      • cardiac dysfunction beginning at 15 days of age   (MGI Ref ID J:150895)
      • cardiac dilation is more or less normal at 5 days of age   (MGI Ref ID J:150895)
  • abnormal heart morphology   (MGI Ref ID J:150895)
    • abnormal heart development
      • loss of cell-cell interaction between myocytes and fibroblasts   (MGI Ref ID J:150895)
      • increased number of fibroblasts and decreased numbers of myocytes   (MGI Ref ID J:150895)
    • abnormal heart ventricle morphology   (MGI Ref ID J:150895)
      • abnormal interventricular septum morphology
        • modestly increased interstitial collagen   (MGI Ref ID J:150895)
      • dilated heart left ventricle   (MGI Ref ID J:150895)
      • thin ventricular wall
        • both anterior and posterior walls of the left ventricle are thin   (MGI Ref ID J:150895)
        • increased interstitial collagen in the free walls of both left and right ventricles   (MGI Ref ID J:150895)
    • decreased heart weight
      • heart weight/body weight and heart weight/tibia length ratios both significantly reduced   (MGI Ref ID J:150895)
  • behavior/neurological phenotype
  • abnormal emotion/affect behavior   (MGI Ref ID J:147420)
    • behavioral despair
      • increased latency to float in a forced swimming test   (MGI Ref ID J:147420)
      • reduced despair behavior   (MGI Ref ID J:147420)
    • increased anxiety-related response
      • more time in the closed arms of an elevated + maze after forced swimming tests   (MGI Ref ID J:147420)
  • abnormal learning/memory/conditioning   (MGI Ref ID J:147420)
    • abnormal object recognition memory
      • reduced exploration in initial phase of novel object recognition tests   (MGI Ref ID J:147420)
      • increased exploration in novel object recognition tests   (MGI Ref ID J:148881)
      • abnormal long term object recognition memory
        • reduced object recognition when retested   (MGI Ref ID J:147420)
        • greater object recognition memory   (MGI Ref ID J:148881)
    • abnormal spatial learning
      • longer escape latencies in a Morris water maze   (MGI Ref ID J:147420)
      • shorter time spent in the target quadrant of a Morris water maze   (MGI Ref ID J:147420)
      • slower to relocate platform after it is moved   (MGI Ref ID J:147420)
  • nervous system phenotype
  • abnormal CNS glial cell morphology   (MGI Ref ID J:79142)
    • abnormal astrocyte morphology
      • density fails to increase in response to neurotoxin (6-OHDA) lesioning   (MGI Ref ID J:79142)
    • abnormal microglial cell morphology
      • modest increase in microglial density after haloperidol treatment relative to the increase seen in controls   (MGI Ref ID J:79142)
  • abnormal brain interneuron morphology
    • parvalbumin positive interneurons in the hippocampus suffer less loss in numbers with age   (MGI Ref ID J:148881)
  • abnormal nervous system physiology   (MGI Ref ID J:148881)
    • abnormal neuron physiology
      • age induced increase in oxygen consumption in synaptosomes is attenuated   (MGI Ref ID J:148881)
  • abnormal neuron morphology   (MGI Ref ID J:79142)
    • abnormal axon morphology
      • axon terminal tree is 25% larger in the substantia nigra pars compacta than for controls   (MGI Ref ID J:79142)
      • resistant to the effects of haloperidol treatment on terminal trees   (MGI Ref ID J:79142)
      • neurotoxin lesion results in reduced terminal tree density   (MGI Ref ID J:79142)
  • muscle phenotype
  • abnormal muscle precursor cell migration
    • migration of primary myoblasts is reduced relative to controls   (MGI Ref ID J:131016)
  • abnormal skeletal muscle fiber morphology
    • cross-sectional area of myofibers does not increase after overload of the plantaris muscle by incapacitation of the gastrocnemius, measured 14 and 42 days after overload   (MGI Ref ID J:131016)
    • no change in myonuclear numbers   (MGI Ref ID J:131016)
  • abnormal skeletal muscle satellite cell proliferation
    • proliferation is defective   (MGI Ref ID J:131016)
  • decreased cardiac muscle contractility
    • both fractional shortening and ejection fraction are decreased in adults and at 5 and 15 days of age   (MGI Ref ID J:150895)
    • cardiac dysfunction beginning at 15 days of age   (MGI Ref ID J:150895)
    • cardiac dilation is more or less normal at 5 days of age   (MGI Ref ID J:150895)
  • vision/eye phenotype
  • retinal outer nuclear layer degeneration
    • higher level of apoptosis after retinal separation from the retinal pigment epithelium   (MGI Ref ID J:136895)
    • higher rate of photoreceptor cell death after 1 month   (MGI Ref ID J:136895)
  • skeleton phenotype
  • abnormal bone healing
    • callus formed after bone fracture is denser after 2 weeks than is true in controls   (MGI Ref ID J:141482)
    • tissue mineral density is less at 4 and 6 weeks after injury than for controls   (MGI Ref ID J:141482)
    • greater collagen content at 2 weeks after fracture but not at 4 or 6 weeks   (MGI Ref ID J:141482)
  • decreased bone mineral density
    • mineral density of cortical bone reduced   (MGI Ref ID J:141482)
    • reduced crystallinity relative to controls   (MGI Ref ID J:141482)
    • reduced mineral/matrix ratio in cortical bone at both 2 and 4 weeks   (MGI Ref ID J:141482)
  • tumorigenesis
  • decreased incidence of tumors by chemical induction
    • reduced incidence of hepatocellular cancer in males treated with diethyl nitrosamine relative to incidence in control males   (MGI Ref ID J:122816)
  • liver/biliary system phenotype
  • hepatic necrosis
    • less necrosis resulting from diethyl nitrosamine treatment   (MGI Ref ID J:122816)
  • liver degeneration
    • less hepatic injury in males from treatment with diethyl nitrosamine   (MGI Ref ID J:122816)
    • less apoptosis due to diethyl nitrosamine treatment   (MGI Ref ID J:122816)
    • less compensatory proliferation as a result of diethyl nitrosamine treatment   (MGI Ref ID J:122816)
  • respiratory system phenotype
  • abnormal pulmonary gas exchange
    • elevated respiratory exchange rate in young mice   (MGI Ref ID J:105633)
  • homeostasis/metabolism phenotype
  • abnormal bone healing
    • callus formed after bone fracture is denser after 2 weeks than is true in controls   (MGI Ref ID J:141482)
    • tissue mineral density is less at 4 and 6 weeks after injury than for controls   (MGI Ref ID J:141482)
    • greater collagen content at 2 weeks after fracture but not at 4 or 6 weeks   (MGI Ref ID J:141482)
  • abnormal exercise endurance
    • reduced treadmill endurance   (MGI Ref ID J:105633)
  • abnormal homeostasis   (MGI Ref ID J:105633)
    • abnormal acute phase protein level
      • 100-fold reduction in SAA production by the liver in response to turpentine injection or listeria infection   (MGI Ref ID J:17360)
    • abnormal oxygen consumption
      • oxygen consumption is not maintained at as high a level after 12 minutes of running as in controls   (MGI Ref ID J:105633)
    • increased circulating glucose level
      • elevated basal glucose levels at 8 months but not in younger mice   (MGI Ref ID J:105633)
      • glucose levels do not differ from controls in young mice after 1 hour of exercise   (MGI Ref ID J:105633)
  • decreased incidence of tumors by chemical induction
    • reduced incidence of hepatocellular cancer in males treated with diethyl nitrosamine relative to incidence in control males   (MGI Ref ID J:122816)
  • endocrine/exocrine gland phenotype
  • abnormal involution of the mammary gland
    • develops more slowly   (MGI Ref ID J:125449)
  • digestive/alimentary phenotype
  • increased susceptibility to induced colitis
    • severe erosion of the intestinal epithelium from exposure to 3.5% dextran sodium sulfate   (MGI Ref ID J:79073)
  • integument phenotype
  • abnormal involution of the mammary gland
    • develops more slowly   (MGI Ref ID J:125449)
  • cellular phenotype
  • abnormal muscle precursor cell migration
    • migration of primary myoblasts is reduced relative to controls   (MGI Ref ID J:131016)
  • abnormal skeletal muscle satellite cell proliferation
    • proliferation is defective   (MGI Ref ID J:131016)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Il6tm1Kopf/Il6tm1Kopf

        B6.129S2-Il6tm1Kopf/J
  • immune system phenotype
  • abnormal interleukin-6 secretion
    • intraperitoneal administration of LPS does not induce production of Il6 in the livers of mutants compared to wild-type where expression is increase   (MGI Ref ID J:109359)
  • decreased interferon-gamma secretion
    • after restimulation of spleen cells with keyhole limpet hemocyanin one week following immunization of mutant mice, reduced interferon gamma production is observed   (MGI Ref ID J:123351)
  • decreased pro-B cell number
    • the percentage of CD19+ B cell progenitors in the bone marrow is decreased from 58% to 35%   (MGI Ref ID J:117320)
  • decreased susceptibility to induced arthritis
    • mice treated with collagen II exhibit a lack of disease incident with normal joints compared with wild-type mice   (MGI Ref ID J:208213)
  • increased interleukin-4 secretion
    • after restimulation of spleen cells with keyhole limpet hemocyanin one week following immunization of mutant mice, enhanced Il-4 secretion is observed   (MGI Ref ID J:123351)
  • homeostasis/metabolism phenotype
  • abnormal glucose homeostasis
    • inhibition of hepatic glucose production by ICV infusion of insulin is attenuated   (MGI Ref ID J:109359)
    • inhibition of hepatic glucose production assessed by a euglycemic hyperinsulinemic clamp is also attenuated   (MGI Ref ID J:109359)
    • decreased glucagon secretion
      • decreased fasting glucagon levels on a high fat diet   (MGI Ref ID J:139138)
    • decreased insulin secretion
      • decreased fasting insulin levels on a high fat diet   (MGI Ref ID J:139138)
    • impaired glucose tolerance
      • impaired glucose tolerance on a high fat diet   (MGI Ref ID J:139138)
  • increased body temperature   (MGI Ref ID J:105279)
    • injection of Il1beta results in body temperature elevation by about 0.5C   (MGI Ref ID J:136166)
  • hematopoietic system phenotype
  • decreased pro-B cell number
    • the percentage of CD19+ B cell progenitors in the bone marrow is decreased from 58% to 35%   (MGI Ref ID J:117320)
  • behavior/neurological phenotype
  • abnormal emotion/affect behavior   (MGI Ref ID J:146951)
    • behavioral despair
      • increased latency to "give up" in a forced swim test   (MGI Ref ID J:146951)
    • increased anxiety-related response
      • less time spent in the illuminated areas of a light-dark box   (MGI Ref ID J:146951)
      • significantly decreased time spent in the open arms of an elevated maze   (MGI Ref ID J:96218)
      • significantly decreased number of entries into the open arms of an elevated maze   (MGI Ref ID J:96218)
    • increased fear-related response
      • lower latency to escape adverse stimuli   (MGI Ref ID J:146951)
      • fewer failures to escape adverse stimuli   (MGI Ref ID J:146951)
  • abnormal sleep pattern
    • injection of Il1beta results in reduced dark phase wakefulness   (MGI Ref ID J:136166)
    • injection of Il1beta results in increased non REM sleep   (MGI Ref ID J:136166)
    • increased time in non-REM sleep after sleep deprivation persists longer than for controls but increase in time is equivalent   (MGI Ref ID J:105279)
    • abnormal frequency of paradoxical sleep
      • 30% increased time in REM sleep over a 24 hour period   (MGI Ref ID J:105279)
      • most extra REM sleep occurs in the light cycle   (MGI Ref ID J:105279)
      • length of REM bouts is normal but number of bouts increases   (MGI Ref ID J:105279)
  • hyperactivity
    • increased locomotor activity in open field tests   (MGI Ref ID J:96218)
  • endocrine/exocrine gland phenotype
  • abnormal pancreatic alpha cell morphology
    • alpha cell mass fails to increase on a high fat diet as it does in controls   (MGI Ref ID J:139138)
  • decreased glucagon secretion
    • decreased fasting glucagon levels on a high fat diet   (MGI Ref ID J:139138)
  • decreased insulin secretion
    • decreased fasting insulin levels on a high fat diet   (MGI Ref ID J:139138)
  • skeleton phenotype
  • decreased susceptibility to induced arthritis
    • mice treated with collagen II exhibit a lack of disease incident with normal joints compared with wild-type mice   (MGI Ref ID J:208213)

Il6tm1Kopf/Il6tm1Kopf

        involves: 129S2/SvPas
  • mortality/aging
  • increased susceptibility to bacterial infection induced morbidity/mortality
    • 60% mortality at day 12 after inoculation with C. rodentium   (MGI Ref ID J:161073)
  • immune system phenotype
  • abnormal T cell physiology
    • mice challenged with Staphylococcus epidermidis cell-free supernatant exhibit impaired T cells (including CD4+, Th1, and Th17 cells) recruitment and production of IL17a compared with similarly treated wild-type mice   (MGI Ref ID J:159479)
  • abnormal inflammatory response
    • following carrageenan induced inflammation, mice exhibit impaired neutrophil resolution after 7 days and delayed macrophage infiltration compared to in similarly treated wild-type mice   (MGI Ref ID J:160966)
  • decreased interleukin-17 secretion
    • mice challenged with Staphylococcus epidermidis cell-free supernatant exhibit fewer IL17a producing cells compared to in similarly treated wild-type mice   (MGI Ref ID J:159479)
  • increased susceptibility to bacterial infection induced morbidity/mortality
    • 60% mortality at day 12 after inoculation with C. rodentium   (MGI Ref ID J:161073)
  • homeostasis/metabolism phenotype
  • decreased susceptibility to injury
    • following exposure to acid-induced acute lung injury, mice exhibit alleviated symptoms compared to wild-type mice   (MGI Ref ID J:145306)
    • 24 hours after scalpel cortex injury, mice exhibit reduced microglial and astrocyte reaction compared with similarly treated wild-type mice   (MGI Ref ID J:89814)
  • delayed wound healing
    • at healing wounds, mice exhibit delayed re-epithelialization, formation of granulation tissue, macrophage infiltration, fibrin clearance, and vascularization compared with wild-type mice   (MGI Ref ID J:160966)
  • impaired wound healing
    • wounds become expanded beyond the boundaries of the original wound unlike in wild-type mice   (MGI Ref ID J:160966)
  • liver/biliary system phenotype
  • abnormal oval cell physiology
    • modestly reduced oval cell response to a choline deficient diet and ethionine in the drinking water   (MGI Ref ID J:66448)
  • nervous system phenotype
  • abnormal glial cell morphology
    • 24 hours after scalpel cortex injury, mice exhibit reduced microglial and astrocyte reaction compared with similarly treated wild-type mice   (MGI Ref ID J:89814)
  • hematopoietic system phenotype
  • abnormal T cell physiology
    • mice challenged with Staphylococcus epidermidis cell-free supernatant exhibit impaired T cells (including CD4+, Th1, and Th17 cells) recruitment and production of IL17a compared with similarly treated wild-type mice   (MGI Ref ID J:159479)

Il6tm1Kopf/Il6tm1Kopf

        involves: 129S2/SvPas * C57BL/6J * CE/J
  • behavior/neurological phenotype
  • seizures
    • a substantial proportion of homozygotes develop generalized seizures after 250 days of age   (MGI Ref ID J:63197)
  • nervous system phenotype
  • seizures
    • a substantial proportion of homozygotes develop generalized seizures after 250 days of age   (MGI Ref ID J:63197)
View Research Applications

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

Cancer Research
Growth Factors/Receptors/Cytokines

Hematological Research
Immunological Defects

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
      experimental allergic encephalomyelitis (EAE)
CD Antigens, Antigen Receptors, and Histocompatibility Markers
      genes regulating susceptibility to infectious disease and endotoxin
Growth Factors/Receptors/Cytokines
Immunodeficiency
Inflammation
Intracellular Signaling Molecules
Lymphoid Tissue Defects

Internal/Organ Research
Lymphoid Tissue Defects
Wound Healing
      delayed/impaired

Research Tools
Cancer Research
Immunology, Inflammation and Autoimmunity Research
      genes regulating susceptibility to infectious disease and endotoxin

Il6tm1Kopf related

Cancer Research
Growth Factors/Receptors/Cytokines

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Il6tm1Kopf
Allele Name targeted mutation 1, Manfred Kopf
Allele Type Targeted (Null/Knockout)
Common Name(s) IL-6 KO; IL-6-; Il6-; Il6tm1Koe; Il6tm1Kopf;
Mutation Made ByDr. Manfred Kopf,   ETH Zurich
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Il6, interleukin 6
Chromosome 5
Gene Common Name(s) BSF2; HGF; HSF; IFNB2; IL-6; ILg6; Il-6;
Molecular Note A neomycin selection cassette was inserted into exon 2. RT-PCR experiments on RNA derived from LPS-stimulated macrophages of homozygous mice demonstrated that no detectable transcript was produced from this allele. ELISA and bioassay experiments confirmed that no functional protein was made in homozygous mice. [MGI Ref ID J:17360]

Genotyping

Genotyping Information

Genotyping Protocols

Il6tm1Kopf MCA, Melt Curve Analysis
Il6tm1Kopf, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kopf M; Baumann H; Freer G; Freudenberg M; Lamers M; Kishimoto T; Zinkernagel R; Bluethmann H; Kohler G. 1994. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368(6469):339-42. [PubMed: 8127368]  [MGI Ref ID J:17360]

Additional References

Cole N; Krockenberger M; Bao S; Beagley KW; Husband AJ; Willcox M. 2001. Effects of Exogenous Interleukin-6 during Pseudomonas aeruginosa Corneal Infection. Infect Immun 69(6):4116-9. [PubMed: 11349084]  [MGI Ref ID J:69543]

Gallucci RM; Simeonova PP; Matheson JM; Kommineni C; Guriel JL; Sugawara T; Luster MI. 2000. Impaired cutaneous wound healing in interleukin-6-deficient and immunosuppressed mice FASEB J 14(15):2525-31. [PubMed: 11099471]  [MGI Ref ID J:66089]

Hilbert DM; Kopf M; Mock BA; Kohler G; Rudikoff S. 1995. Interleukin 6 is essential for in vivo development of B lineage neoplasms. J Exp Med 182(1):243-8. [PubMed: 7790819]  [MGI Ref ID J:26249]

Lin T; Bost KL. 2004. STAT3 activation in macrophages following infection with Salmonella. Biochem Biophys Res Commun 321(4):828-34. [PubMed: 15358102]  [MGI Ref ID J:91740]

Wang Q; Fang CH; Hasselgren PO. 2001. Intestinal permeability is reduced and IL-10 levels are increased in septic IL-6 knockout mice. Am J Physiol Regul Integr Comp Physiol 281(3):R1013-23. [PubMed: 11507020]  [MGI Ref ID J:71507]

van der Poll T; Keogh CV; Guirao X; Buurman WA; Kopf M; Lowry SF. 1997. Interleukin-6 gene-deficient mice show impaired defense against pneumococcal pneumonia. J Infect Dis 176(2):439-44. [PubMed: 9237710]  [MGI Ref ID J:41791]

Il6tm1Kopf related

Akasheh RT; Pini M; Pang J; Fantuzzi G. 2013. Increased adiposity in annexin A1-deficient mice. PLoS One 8(12):e82608. [PubMed: 24312665]  [MGI Ref ID J:209746]

Ancrile B; Lim KH; Counter CM. 2007. Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev 21(14):1714-9. [PubMed: 17639077]  [MGI Ref ID J:123152]

Andris F; Denanglaire S; Baus E; Rongvaux A; Steuve J; Flavell RA; Leo O. 2011. Metabolic stress boosts humoral responses in vivo independently of inflammasome and inflammatory reaction. J Immunol 186(4):2245-53. [PubMed: 21248260]  [MGI Ref ID J:169140]

Angeli V; Faveeuw C; Delerive P; Fontaine J; Barriera Y; Franchimont N; Staels B; Capron M; Trottein F. 2001. Schistosoma mansoni induces the synthesis of IL-6 in pulmonary microvascular endothelial cells: role of IL-6 in the control of lung eosinophilia during infection. Eur J Immunol 31(9):2751-61. [PubMed: 11536174]  [MGI Ref ID J:71675]

Anguita J; Rincon M; Samanta S; Barthold SW; Flavell RA; Fikrig E. 1998. Borrelia burgdorferi-infected, interleukin-6-deficient mice have decreased Th2 responses and increased lyme arthritis. J Infect Dis 178(5):1512-5. [PubMed: 9780277]  [MGI Ref ID J:51191]

Ankathatti Munegowda M; Xu S; Freywald A; Xiang J. 2012. CD4+ Th2 cells function alike effector Tr1 and Th1 cells through the deletion of a single cytokine IL-6 and IL-10 gene. Mol Immunol 51(2):143-9. [PubMed: 22424785]  [MGI Ref ID J:184874]

Aoki R; Kawamura T; Goshima F; Ogawa Y; Nakae S; Nakao A; Moriishi K; Nishiyama Y; Shimada S. 2013. Mast Cells Play a Key Role in Host Defense against Herpes Simplex Virus Infection through TNF-alpha and IL-6 Production. J Invest Dermatol 133(9):2170-9. [PubMed: 23528820]  [MGI Ref ID J:200049]

Arima Y; Harada M; Kamimura D; Park JH; Kawano F; Yull FE; Kawamoto T; Iwakura Y; Betz UA; Marquez G; Blackwell TS; Ohira Y; Hirano T; Murakami M. 2012. Regional neural activation defines a gateway for autoreactive T cells to cross the blood-brain barrier. Cell 148(3):447-57. [PubMed: 22304915]  [MGI Ref ID J:181336]

Armario A; Hernandez J; Bluethmann H; Hidalgo J. 1998. IL-6 deficiency leads to increased emotionality in mice: evidence in transgenic mice carrying a null mutation for IL-6. J Neuroimmunol 92(1-2):160-9. [PubMed: 9916891]  [MGI Ref ID J:53626]

Arocena AR; Onofrio LI; Pellegrini AV; Carrera Silva AE; Paroli A; Cano RC; Aoki MP; Gea S. 2014. Myeloid-derived suppressor cells are key players in the resolution of inflammation during a model of acute infection. Eur J Immunol 44(1):184-94. [PubMed: 24166778]  [MGI Ref ID J:208911]

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Xia M; Liu J; Wu X; Liu S; Li G; Han C; Song L; Li Z; Wang Q; Wang J; Xu T; Cao X. 2013. Histone methyltransferase Ash1l suppresses interleukin-6 production and inflammatory autoimmune diseases by inducing the ubiquitin-editing enzyme A20. Immunity 39(3):470-81. [PubMed: 24012418]  [MGI Ref ID J:208213]

Xing Z; Gauldie J; Cox G; Baumann H; Jordana M; Lei XF; Achong MK. 1998. IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 101(2):311-20. [PubMed: 9435302]  [MGI Ref ID J:118763]

Yang CY; Leung PS; Yang GX; Kenny TP; Zhang W; Coppel R; Norman GL; Ansari AA; Mackay IR; Worman HJ; Gershwin ME. 2012. Epitope-specific anti-nuclear antibodies are expressed in a mouse model of primary biliary cirrhosis and are cytokine-dependent. Clin Exp Immunol 168(3):261-7. [PubMed: 22519587]  [MGI Ref ID J:184866]

Yang J; Chen J; Yan J; Zhang L; Chen G; He L; Wang Y. 2012. Effect of interleukin 6 deficiency on renal interstitial fibrosis. PLoS One 7(12):e52415. [PubMed: 23272241]  [MGI Ref ID J:195642]

Yang R; Han X; Uchiyama T; Watkins SK; Yaguchi A; Delude RL; Fink MP. 2003. IL-6 is essential for development of gut barrier dysfunction after hemorrhagic shock and resuscitation in mice. Am J Physiol Gastrointest Liver Physiol 285(3):G621-9. [PubMed: 12773301]  [MGI Ref ID J:85434]

Yang S; Ryu JH; Oh H; Jeon J; Kwak JS; Kim JH; Kim HA; Chun CH; Chun JS. 2013. NAMPT (visfatin), a direct target of hypoxia-inducible factor-2alpha, is an essential catabolic regulator of osteoarthritis. Ann Rheum Dis :. [PubMed: 24347567]  [MGI Ref ID J:206286]

Yang X; Ricciardi BF; Hernandez-Soria A; Shi Y; Pleshko Camacho N; Bostrom MP. 2007. Callus mineralization and maturation are delayed during fracture healing in interleukin-6 knockout mice. Bone 41(6):928-36. [PubMed: 17921078]  [MGI Ref ID J:141482]

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]

Yimin; Kohanawa M; Minagawa T. 2003. Up-regulation of granulomatous inflammation in interleukin-6 knockout mice infected with Rhodococcus aurantiacus. Immunology 110(4):501-6. [PubMed: 14632648]  [MGI Ref ID J:113603]

Yoh K; Morito N; Ojima M; Shibuya K; Yamashita Y; Morishima Y; Ishii Y; Kusakabe M; Nishikii H; Fujita A; Matsunaga E; Okamura M; Hamada M; Suto A; Nakajima H; Shibuya A; Yamagata K; Takahashi S. 2012. Overexpression of RORgammat under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice. Eur J Immunol 42(8):1999-2009. [PubMed: 22623033]  [MGI Ref ID J:187853]

Yu M; Zheng X; Witschi H; Pinkerton KE. 2002. The role of interleukin-6 in pulmonary inflammation and injury induced by exposure to environmental air pollutants. Toxicol Sci 68(2):488-97. [PubMed: 12151646]  [MGI Ref ID J:126238]

Zenewicz LA; Yancopoulos GD; Valenzuela DM; Murphy AJ; Karow M; Flavell RA. 2007. Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27(4):647-59. [PubMed: 17919941]  [MGI Ref ID J:126103]

Zhang H; Ching S; Chen Q; Li Q; An Y; Quan N. 2008. Localized inflammation in peripheral tissue signals the CNS for sickness response in the absence of interleukin-1 and cyclooxygenase-2 in the blood and brain. Neuroscience 157(4):895-907. [PubMed: 18950689]  [MGI Ref ID J:144882]

Zhang H; Wang HY; Bassel-Duby R; Maass DL; Johnston WE; Horton JW; Tao W. 2007. Role of interleukin-6 in cardiac inflammation and dysfunction after burn complicated by sepsis. Am J Physiol Heart Circ Physiol 292(5):H2408-16. [PubMed: 17220181]  [MGI Ref ID J:125958]

Zhang J; Alcaide P; Liu L; Sun J; He A; Luscinskas FW; Shi GP. 2011. Regulation of endothelial cell adhesion molecule expression by mast cells, macrophages, and neutrophils. PLoS One 6(1):e14525. [PubMed: 21264293]  [MGI Ref ID J:169463]

Zhang J; Zhu Y; Zhan G; Fenik P; Panossian L; Wang MM; Reid S; Lai D; Davis JG; Baur JA; Veasey S. 2014. Extended wakefulness: compromised metabolics in and degeneration of locus ceruleus neurons. J Neurosci 34(12):4418-31. [PubMed: 24647961]  [MGI Ref ID J:210306]

Zhang W; Tsuda M; Yang GX; Tsuneyama K; He XS; Ansari AA; Ridgway WM; Coppel RL; Lian ZX; Leung PS; Gershwin ME. 2012. Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFbeta receptor II. PLoS One 7(11):e49413. [PubMed: 23145171]  [MGI Ref ID J:194795]

Zhang X; Goel T; Goodfield LL; Muse SJ; Harvill ET. 2011. Decreased leukocyte accumulation and delayed Bordetella pertussis clearance in IL-6-/- mice. J Immunol 186(8):4895-904. [PubMed: 21398615]  [MGI Ref ID J:172453]

Zhang X; Munegowda MA; Yuan J; Wei Y; Xiang J. 2010. Optimal TLR9 signal converts tolerogenic CD4-8- DCs into immunogenic ones capable of stimulating antitumor immunity via activating CD4+ Th1/Th17 and NK cell responses. J Leukoc Biol 88(2):393-403. [PubMed: 20466823]  [MGI Ref ID J:163943]

Zhang Y; Yan W; Collins MA; Bednar F; Rakshit S; Zetter BR; Stanger BZ; Chung I; Rhim AD; di Magliano MP. 2013. Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance. Cancer Res 73(20):6359-74. [PubMed: 24097820]  [MGI Ref ID J:205411]

Zhao L; Melenhorst JJ; Hennighausen L. 2002. Loss of interleukin 6 results in delayed mammary gland involution: a possible role for mitogen-activated protein kinase and not signal transducer and activator of transcription 3. Mol Endocrinol 16(12):2902-12. [PubMed: 12456808]  [MGI Ref ID J:125449]

Zheng Y; Danilenko DM; Valdez P; Kasman I; Eastham-Anderson J; Wu J; Ouyang W. 2007. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445(7128):648-51. [PubMed: 17187052]  [MGI Ref ID J:118261]

Zheng Y; Valdez PA; Danilenko DM; Hu Y; Sa SM; Gong Q; Abbas AR; Modrusan Z; Ghilardi N; de Sauvage FJ; Ouyang W. 2008. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14(3):282-9. [PubMed: 18264109]  [MGI Ref ID J:161073]

Zhong J; Dietzel ID; Wahle P; Kopf M; Heumann R. 1999. Sensory impairments and delayed regeneration of sensory axons in interleukin-6-deficient mice. J Neurosci 19(11):4305-13. [PubMed: 10341234]  [MGI Ref ID J:55028]

Zhong Y; Cantwell A; Dube PH. 2010. Transforming growth factor beta and CD25 are important for controlling systemic dissemination following Yersinia enterocolitica infection of the gut. Infect Immun 78(9):3716-25. [PubMed: 20584975]  [MGI Ref ID J:163014]

Zhou J; Tang PC; Qin L; Gayed PM; Li W; Skokos EA; Kyriakides TR; Pober JS; Tellides G. 2010. CXCR3-dependent accumulation and activation of perivascular macrophages is necessary for homeostatic arterial remodeling to hemodynamic stresses. J Exp Med 207(9):1951-66. [PubMed: 20733031]  [MGI Ref ID J:165720]

Zhou L; Ivanov II; Spolski R; Min R; Shenderov K; Egawa T; Levy DE; Leonard WJ; Littman DR. 2007. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8(9):967-74. [PubMed: 17581537]  [MGI Ref ID J:124293]

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Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryThis strain is maintained by mating homozygous siblings. Expected coat color from breeding:Black
Mating SystemHomozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $239.00Female or MaleHomozygous for Il6tm1Kopf  
Price per Pair (US dollars $)Pair Genotype
$478.00Homozygous for Il6tm1Kopf x Homozygous for Il6tm1Kopf  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $310.70Female or MaleHomozygous for Il6tm1Kopf  
Price per Pair (US dollars $)Pair Genotype
$621.40Homozygous for Il6tm1Kopf x Homozygous for Il6tm1Kopf  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


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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JAX® Mice
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Tel: 1-800-422-6423 or 1-207-288-5845
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Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Notice regarding distribution of this strain.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

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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, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, 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 JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS 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 JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or services by JACKSON.


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