Strain Name:

B6.B10ScN-Tlr4lps-del/JthJ

Stock Number:

007227

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Availability:

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    The Tlr4Lps-del spontaneous mutation exhibits a defective response to LPS stimulation and affects Toll signaling pathways involved with inflammation, including susceptibility to various bacterial infections, effects of tissue ischemia (including cerebral and retinal ischemia), myocardial infarction, neurodegeneration, and tumor immune responses.

Description

Strain Information

Type Congenic; Spontaneous Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemHomozygote x Homozygote         (Female x Male)   28-APR-09
Specieslaboratory mouse
Background Strain C57BL/6
Donor Strain C57BL/10ScN
H2 Haplotypeb
GenerationN6+N1F12 (12-DEC-13)
Generation Definitions

Appearance
black
Related Genotype: a/a

Description
    The stimulation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) induces the release of proinflammatory cytokines that activate immune responses. The Tlr4Lps-del spontaneous mutation corresponds to a 74723 bp deletion that completely removes the Tlr4 coding sequence. No mRNA or protein is expressed. Homozygous mutants exhibit a defective response to LPS stimulation. The functionally similar Tlr4Lps-d mutation found in C3H/HeJ mice (#000659) is a point mutation that causes an amino acid substitution.
    Tlr4 -deficient mice display significantly reduced expression of proinflammatory genes compared to controls 24 h after reperfusion triggered by retinal ischemic injury. These include transcriptional factor p65 (Rela), tumor necrosis factor (Thf), interleukin 6 (Il6), chemokine (C-C motif) ligand 2 (Ccl2), chemokine (C-C motif) ligand 5 (Ccl5), chemokine (C-X-C motif) ligand 10 (Cxcl10), cytochrome b-245, beta polypeptide (Cybb), nitric oxide synthase 2 (Nos2), and intercellular adhesion molecule 1 (Icam1) (Dvoriantchikova et al., 2010).
    The effect of TLR4 on tumor progression appears to depend on which cells TLR4 resides and the particular ligand involved. For example, enhanced prostrate tumor progression as a result of TLR4 response to a tumor-derived ligand such as Peroxiredoxin is not seen in the Tlr4 deficient mutant mice (Riddell et al., 2011). Conversely, tumor inhibition seen in wild type mice when B16 melanoma cells were stimulated in vitro with LPS was not seen in mutant mice (Nunez et al., 2012).
    TLR4 signaling may also act as innate neuroprotective mechanism through clearance of alpha-synuclein as TLR4 ablation impairs the phagocytic response of microglia to alpha-synuclein and enhances neurodegeneration (Stefanova et al. 2011).

Development
Abnormal response to lipopolysaccharide was observed in the inbred strain C57BL/10ScN in the 1970s. The phenotype was subsequently identified as a mutation in the Tlr4 gene. This strain originated from the C57BL/10ScN colony at NCI Frederick and was transferred to the laboratory of Dr. James Thomas, University of Texas Southwestern Medical Center. The allele was introgressed into C57BL/6 by backcrossing for at least five generations. The strain was donated to The Jackson Laboratory Repository in 2008.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Tlr4lps-del allele
003752   C57BL/10ScNJ
View Strains carrying   Tlr4lps-del     (1 strain)

Strains carrying other alleles of Tlr4
024872   B6(Cg)-Tlr4tm1.1Karp/J
000029   BXD29-Tlr4lps-2J/J
002930   C.C3-Tlr4Lps-d/J
005973   C3Bir.129P2(B6)-Il10C3Bir/LtJ
004326   C3Bir.129P2(B6)-Il10tm1Cgn/Lt
003968   C3Bir.129P2(B6)-Il10tm1Cgn/LtJ
000659   C3H/HeJ
005972   C3H/HeJBirLtJ
View Strains carrying other alleles of Tlr4     (8 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Toll-Like Receptor 4; TLR4
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Macular Degeneration, Age-Related, 10; ARMD10   (TLR4)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Tlr4lps-del/Tlr4lps-del

        C57BL/10ScCr
  • immune system phenotype
  • abnormal cytokine secretion
    • higher levels of Th1 and Th2 cytokines secreted at 4 weeks after infection with Leishmania major than in controls   (MGI Ref ID J:88996)
  • abnormal macrophage physiology
    • poor activation of macrophage by Leishmania major   (MGI Ref ID J:88996)
  • increased susceptibility to bacterial infection
    • response to endotoxin (LPS) prevented   (MGI Ref ID J:51522)
    • Leishmania major parasitic loads significantly higher than controls starting 24 hours after infection and persisting to 11 weeks after infection when controls are free of parasites   (MGI Ref ID J:88996)
  • behavior/neurological phenotype
  • hyporesponsive to tactile stimuli
    • attenuated mechanical allodynia after nerve injury   (MGI Ref ID J:97819)
  • increased thermal nociceptive threshold
    • attenuated response to heat   (MGI Ref ID J:97819)
  • nervous system phenotype
  • abnormal glial cell physiology
    • glial activation after nerve injury reduced   (MGI Ref ID J:97819)
  • cardiovascular system phenotype
  • decreased response of heart to induced stress
    • exhibit reduced cardiac hypertrophy following pressure overload compared to controls   (MGI Ref ID J:106358)
  • homeostasis/metabolism phenotype
  • decreased susceptibility to injury
    • reduced spinal expression of TNF alpha, IFN gamma, IL-6 and IL-1 after injury   (MGI Ref ID J:97819)
    • glial activation after nerve injury reduced   (MGI Ref ID J:97819)
    • decreased response of heart to induced stress
      • exhibit reduced cardiac hypertrophy following pressure overload compared to controls   (MGI Ref ID J:106358)
  • integument phenotype
  • hyporesponsive to tactile stimuli
    • attenuated mechanical allodynia after nerve injury   (MGI Ref ID J:97819)
  • increased thermal nociceptive threshold
    • attenuated response to heat   (MGI Ref ID J:97819)
  • hematopoietic system phenotype
  • abnormal macrophage physiology
    • poor activation of macrophage by Leishmania major   (MGI Ref ID J:88996)

Tlr4lps-del/Tlr4lps-del

        C57BL/10ScN
  • digestive/alimentary phenotype
  • rectal hemorrhage
    • rectal bleeding after 7 days of dextran sodium sulfate treatment is reduced relative to controls   (MGI Ref ID J:37271)
  • immune system phenotype
  • increased spleen weight
    • spleen weight elevated with dextran sodium sulfate treatment relative to controls   (MGI Ref ID J:37271)
  • respiratory system phenotype
  • abnormal pulmonary alveolar duct morphology
    • enlarged air spaces distal to the terminal bronchioles   (MGI Ref ID J:114985)
  • abnormal pulmonary alveolus morphology
    • destruction of normal alveolar structures   (MGI Ref ID J:114985)
  • enlarged lung
    • significantly increased lung volume at 3 months of age in contrast to normal body weights through 12 months   (MGI Ref ID J:114985)
  • skeleton phenotype
  • increased bone mass
    • larger bones at 20-24 weeks of age   (MGI Ref ID J:118467)
  • increased bone mineral content
    • greater mineral content at 20-24 weeks   (MGI Ref ID J:118467)
  • adipose tissue phenotype
  • decreased percent body fat
    • 70% less body fat   (MGI Ref ID J:118467)
  • vision/eye phenotype
  • abnormal retinal layer morphology   (MGI Ref ID J:141070)
    • abnormal retinal pigment epithelium morphology
      • increased number of proliferating cells in the retinal pigment cell layer at 6 days of age   (MGI Ref ID J:141070)
    • abnormal retinal rod cell morphology
      • increased differentiation of rod photoreceptors at around 13 days of age   (MGI Ref ID J:141070)
      • growth factor treatment enhances proliferation   (MGI Ref ID J:141070)
  • abnormal retinal progenitor cell morphology
    • more proliferating cells in the retina at 6 days of age   (MGI Ref ID J:141070)
    • neuronal differentiation of precursors   (MGI Ref ID J:141070)
    • FGF-2 injection is required for a similar effect after 15 days of age   (MGI Ref ID J:141070)
  • abnormal retinal rod bipolar cell morphology
    • increased differentiation at around 13 days of age   (MGI Ref ID J:141070)
    • growth factor treatment enhances proliferation   (MGI Ref ID J:141070)
  • nervous system phenotype
  • abnormal retinal rod bipolar cell morphology
    • increased differentiation at around 13 days of age   (MGI Ref ID J:141070)
    • growth factor treatment enhances proliferation   (MGI Ref ID J:141070)
  • abnormal retinal rod cell morphology
    • increased differentiation of rod photoreceptors at around 13 days of age   (MGI Ref ID J:141070)
    • growth factor treatment enhances proliferation   (MGI Ref ID J:141070)
  • pigmentation phenotype
  • abnormal retinal pigment epithelium morphology
    • increased number of proliferating cells in the retinal pigment cell layer at 6 days of age   (MGI Ref ID J:141070)
  • hematopoietic system phenotype
  • increased spleen weight
    • spleen weight elevated with dextran sodium sulfate treatment relative to controls   (MGI Ref ID J:37271)
  • cardiovascular system phenotype
  • rectal hemorrhage
    • rectal bleeding after 7 days of dextran sodium sulfate treatment is reduced relative to controls   (MGI Ref ID J:37271)
  • growth/size/body phenotype
  • decreased percent body fat
    • 70% less body fat   (MGI Ref ID J:118467)

Tlr4lps-del/Tlr4lps-del

        involves: C57BL/10ScN
  • immune system phenotype
  • abnormal tumor necrosis factor level
    • diminished TNF alpha expression after 90 minutes of liver ischemia followed by 6 hours of reperfusion   (MGI Ref ID J:114368)
  • decreased interleukin-10 secretion
    • production is suppressed in response to E coli with or without adenosine   (MGI Ref ID J:147023)
  • decreased interleukin-6 secretion
    • production is suppressed in response to E coli   (MGI Ref ID J:147023)
  • homeostasis/metabolism phenotype
  • abnormal circulating enzyme level
    • myeloperoxidase levels are reduced after 90 minutes of liver ischemia followed by 6 hours of reperfusion   (MGI Ref ID J:114368)
    • increased HO-1 expression   (MGI Ref ID J:114368)
    • decreased circulating alanine transaminase level
      • serum levels decreased after 90 minutes of liver ischemia followed by 6 hours of reperfusion   (MGI Ref ID J:114368)
  • abnormal tumor necrosis factor level
    • diminished TNF alpha expression after 90 minutes of liver ischemia followed by 6 hours of reperfusion   (MGI Ref ID J:114368)
  • nervous system phenotype
  • CNS ischemia
    • improved neurological score relative to controls after ischemia/reperfusion   (MGI Ref ID J:148091)
    • reduced infarct size relative to controls at 24 hours after ischemia/reperfusion   (MGI Ref ID J:148091)
  • abnormal neuron differentiation
    • improved differentiation of progenitor cells into neurons   (MGI Ref ID J:129957)
    • survival of newly formed neurons is reduced   (MGI Ref ID J:129957)
  • cellular phenotype
  • abnormal neuron differentiation
    • improved differentiation of progenitor cells into neurons   (MGI Ref ID J:129957)
    • survival of newly formed neurons is reduced   (MGI Ref ID J:129957)
View Research Applications

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

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
      Tlr deficiency
Immunodeficiency
      Tlr deficiency
Inflammation
      Tlr deficiency

Tlr4lps-del related

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
      Tlr deficiency
Immunodeficiency
      Tlr deficiency
Inflammation
      Tlr deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tlr4lps-del
Allele Name defective lipopolysaccharide response, deletion
Allele Type Spontaneous
Common Name(s) TLR4-KO; TLR4lps-; Tlr4-;
Strain of OriginC57BL/10ScN
Gene Symbol and Name Tlr4, toll-like receptor 4
Chromosome 4
Gene Common Name(s) ARMD10; CD284; Lps; RAS-like, family 2, locus 8; Rasl2-8; TLR-4; TOLL; lipopolysaccharide response;
General Note C57BL/10ScN, C57BL/10ScNJ, and C57BL10/ScCr mice carry this allele.
Molecular Note This allele has been characterized by lack of mRNA owing to a deletion of the locus. 74723bp of genomic DNA sequence have been removed, apparently encompasing only the Tlr4 gene. [MGI Ref ID J:122203] [MGI Ref ID J:51522]

Genotyping

Genotyping Information

Genotyping Protocols

Tlr4lps-del, Melt Curve Analysis
Tlr4lps-del, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Poltorak A; He X; Smirnova I; Liu MY; Huffel CV; Du X; Birdwell D; Alejos E; Silva M; Galanos C; Freudenberg M; Ricciardi-Castagnoli P; Layton B; Beutler B. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282(5396):2085-8. [PubMed: 9851930]  [MGI Ref ID J:51522]

Vogel SN; Hansen CT; Rosenstreich DL. 1979. Characterization of a congenitally LPS-resistant, athymic mouse strain. J Immunol 122(2):619-22. [PubMed: 368244]  [MGI Ref ID J:6086]

Additional References

Tlr4lps-del related

Aachoui Y; Leaf IA; Hagar JA; Fontana MF; Campos CG; Zak DE; Tan MH; Cotter PA; Vance RE; Aderem A; Miao EA. 2013. Caspase-11 protects against bacteria that escape the vacuole. Science 339(6122):975-8. [PubMed: 23348507]  [MGI Ref ID J:193387]

Agace W; Hedges S; Svanborg C. 1992. Lps genotype in the C57 black mouse background and its influence on the interleukin-6 response to E. coli urinary tract infection. Scand J Immunol 35(5):531-8. [PubMed: 1579857]  [MGI Ref ID J:3436]

Amiel E; Alonso A; Uematsu S; Akira S; Poynter ME; Berwin B. 2009. Pivotal Advance: Toll-like receptor regulation of scavenger receptor-A-mediated phagocytosis. J Leukoc Biol 85(4):595-605. [PubMed: 19112093]  [MGI Ref ID J:146918]

An CH; Wang XM; Lam HC; Ifedigbo E; Washko GR; Ryter SW; Choi AM. 2012. TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema. Am J Physiol Lung Cell Mol Physiol 303(9):L748-57. [PubMed: 22983353]  [MGI Ref ID J:193661]

Andonegui G; Kerfoot SM; McNagny K; Ebbert KV; Patel KD; Kubes P. 2005. Platelets express functional Toll-like receptor-4. Blood 106(7):2417-23. [PubMed: 15961512]  [MGI Ref ID J:119375]

Babelova A; Moreth K; Tsalastra-Greul W; Zeng-Brouwers J; Eickelberg O; Young MF; Bruckner P; Pfeilschifter J; Schaefer RM; Grone HJ; Schaefer L. 2009. Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and P2X receptors. J Biol Chem 284(36):24035-48. [PubMed: 19605353]  [MGI Ref ID J:155256]

Beisswenger C; Lysenko ES; Weiser JN. 2009. Early bacterial colonization induces toll-like receptor-dependent transforming growth factor beta signaling in the epithelium. Infect Immun 77(5):2212-20. [PubMed: 19255194]  [MGI Ref ID J:148184]

Benabid R; Wartelle J; Malleret L; Guyot N; Gangloff S; Lebargy F; Belaaouaj A. 2012. Neutrophil elastase modulates cytokine expression: contribution to host defense against Pseudomonas aeruginosa-induced pneumonia. J Biol Chem 287(42):34883-94. [PubMed: 22927440]  [MGI Ref ID J:192139]

Berger SB; Romero X; Ma C; Wang G; Faubion WA; Liao G; Compeer E; Keszei M; Rameh L; Wang N; Boes M; Regueiro JR; Reinecker HC; Terhorst C. 2010. SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages. Nat Immunol 11(10):920-7. [PubMed: 20818396]  [MGI Ref ID J:164685]

Bhattacharyya S; Dudeja PK; Tobacman JK. 2008. Lipopolysaccharide activates NF-kappaB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 295(4):G784-90. [PubMed: 18718996]  [MGI Ref ID J:142282]

Binck BW; Tsen MF; Islas M; White DJ; Schultz RA; Willis MS; Garcia JV; Horton JW; Thomas JA. 2005. Bone marrow-derived cells contribute to contractile dysfunction in endotoxic shock. Am J Physiol Heart Circ Physiol 288(2):H577-83. [PubMed: 15458952]  [MGI Ref ID J:96165]

Biragyn A; Coscia M; Nagashima K; Sanford M; Young HA; Olkhanud P. 2008. Murine beta-defensin 2 promotes TLR-4/MyD88-mediated and NF-kappaB-dependent atypical death of APCs via activation of TNFR2. J Leukoc Biol 83(4):998-1008. [PubMed: 18192488]  [MGI Ref ID J:134193]

Bosmann M; Haggadone MD; Hemmila MR; Zetoune FS; Sarma JV; Ward PA. 2012. Complement activation product C5a is a selective suppressor of TLR4-induced, but not TLR3-induced, production of IL-27(p28) from macrophages. J Immunol 188(10):5086-93. [PubMed: 22491257]  [MGI Ref ID J:188678]

Bosmann M; Strobl B; Kichler N; Rigler D; Grailer JJ; Pache F; Murray PJ; Muller M; Ward PA. 2014. Tyrosine kinase 2 promotes sepsis-associated lethality by facilitating production of interleukin-27. J Leukoc Biol 96(1):123-31. [PubMed: 24604832]  [MGI Ref ID J:212012]

Burch LH; Yang IV; Whitehead GS; Chao FG; Berman KG; Schwartz DA. 2006. The transcriptional response to lipopolysaccharide reveals a role for interferon-gamma in lung neutrophil recruitment. Am J Physiol Lung Cell Mol Physiol 291(4):L677-82. [PubMed: 16766576]  [MGI Ref ID J:144404]

Burns E; Bachrach G; Shapira L; Nussbaum G. 2006. Cutting Edge: TLR2 is required for the innate response to Porphyromonas gingivalis: activation leads to bacterial persistence and TLR2 deficiency attenuates induced alveolar bone resorption. J Immunol 177(12):8296-300. [PubMed: 17142724]  [MGI Ref ID J:140676]

Carnevalli LS; Scognamiglio R; Cabezas-Wallscheid N; Rahmig S; Laurenti E; Masuda K; Jockel L; Kuck A; Sujer S; Polykratis A; Erlacher M; Pasparakis M; Essers MA; Trumpp A. 2014. Improved HSC reconstitution and protection from inflammatory stress and chemotherapy in mice lacking granzyme B. J Exp Med 211(5):769-79. [PubMed: 24752302]  [MGI Ref ID J:211304]

Carpentier PA; Dingman AL; Palmer TD. 2011. Placental TNF-alpha Signaling in Illness-Induced Complications of Pregnancy. Am J Pathol 178(6):2802-10. [PubMed: 21641402]  [MGI Ref ID J:173471]

Caso JR; Pradillo JM; Hurtado O; Lorenzo P; Moro MA; Lizasoain I. 2007. Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation 115(12):1599-608. [PubMed: 17372179]  [MGI Ref ID J:133065]

Chabot S; Wagner JS; Farrant S; Neutra MR. 2006. TLRs regulate the gatekeeping functions of the intestinal follicle-associated epithelium. J Immunol 176(7):4275-83. [PubMed: 16547265]  [MGI Ref ID J:129895]

Chan YR; Liu JS; Pociask DA; Zheng M; Mietzner TA; Berger T; Mak TW; Clifton MC; Strong RK; Ray P; Kolls JK. 2009. Lipocalin 2 is required for pulmonary host defense against Klebsiella infection. J Immunol 182(8):4947-56. [PubMed: 19342674]  [MGI Ref ID J:147498]

Chandrakesan P; Jakkula LU; Ahmed I; Roy B; Anant S; Umar S. 2013. Differential effects of beta-catenin and NF-kappaB interplay in the regulation of cell proliferation, inflammation and tumorigenesis in response to bacterial infection. PLoS One 8(11):e79432. [PubMed: 24278135]  [MGI Ref ID J:209657]

Chen J; Hartono JR; John R; Bennett M; Zhou XJ; Wang Y; Wu Q; Winterberg PD; Nagami GT; Lu CY. 2011. Early interleukin 6 production by leukocytes during ischemic acute kidney injury is regulated by TLR4. Kidney Int 80(5):504-15. [PubMed: 21633411]  [MGI Ref ID J:194804]

Chen J; John R; Richardson JA; Shelton JM; Zhou XJ; Wang Y; Wu QQ; Hartono JR; Winterberg PD; Lu CY. 2011. Toll-like receptor 4 regulates early endothelial activation during ischemic acute kidney injury. Kidney Int 79(3):288-99. [PubMed: 20927041]  [MGI Ref ID J:186890]

Chen J; Matzuk MM; Zhou XJ; Lu CY. 2012. Endothelial pentraxin 3 contributes to murine ischemic acute kidney injury. Kidney Int 82(11):1195-207. [PubMed: 22895517]  [MGI Ref ID J:198404]

Cohen-Sfady M; Pevsner-Fischer M; Margalit R; Cohen IR. 2009. Heat shock protein 60, via MyD88 innate signaling, protects B cells from apoptosis, spontaneous and induced. J Immunol 183(2):890-6. [PubMed: 19561102]  [MGI Ref ID J:151657]

Costalonga M; Zell T. 2007. Lipopolysaccharide enhances in vivo interleukin-2 production and proliferation by naive antigen-specific CD4 T cells via a Toll-like receptor 4-dependent mechanism. Immunology 122(1):124-30. [PubMed: 17484770]  [MGI Ref ID J:125617]

Csoka B; Nemeth ZH; Virag L; Gergely P; Leibovich SJ; Pacher P; Sun CX; Blackburn MR; Vizi ES; Deitch EA; Hasko G. 2007. A2A adenosine receptors and C/EBPbeta are crucially required for IL-10 production by macrophages exposed to Escherichia coli. Blood 110(7):2685-95. [PubMed: 17525287]  [MGI Ref ID J:147023]

Csoka B; Selmeczy Z; Koscso B; Nemeth ZH; Pacher P; Murray PJ; Kepka-Lenhart D; Morris SM Jr; Gause WC; Leibovich SJ; Hasko G. 2012. Adenosine promotes alternative macrophage activation via A2A and A2B receptors. FASEB J 26(1):376-86. [PubMed: 21926236]  [MGI Ref ID J:195612]

D'Avila H; Almeida PE; Roque NR; Castro-Faria-Neto HC; Bozza PT. 2007. Toll-Like Receptor-2-Mediated C-C Chemokine Receptor 3 and Eotaxin-Driven Eosinophil Influx Induced by Mycobacterium bovis BCG Pleurisy. Infect Immun 75(3):1507-11. [PubMed: 17158890]  [MGI Ref ID J:118500]

D'Avila H; Melo RC; Parreira GG; Werneck-Barroso E; Castro-Faria-Neto HC; Bozza PT. 2006. Mycobacterium bovis bacillus Calmette-Guerin induces TLR2-mediated formation of lipid bodies: intracellular domains for eicosanoid synthesis in vivo. J Immunol 176(5):3087-97. [PubMed: 16493068]  [MGI Ref ID J:129415]

Darville T; O'Neill JM; Andrews CW Jr; Nagarajan UM; Stahl L; Ojcius DM. 2003. Toll-like receptor-2, but not Toll-like receptor-4, is essential for development of oviduct pathology in chlamydial genital tract infection. J Immunol 171(11):6187-97. [PubMed: 14634135]  [MGI Ref ID J:106730]

David MD; Cochrane CL; Duncan SK; Schrader JW. 2005. Pure lipopolysaccharide or synthetic lipid A induces activation of p21Ras in primary macrophages through a pathway dependent on Src family kinases and PI3K. J Immunol 175(12):8236-41. [PubMed: 16339563]  [MGI Ref ID J:122258]

Davis MJ; Gregorka B; Gestwicki JE; Swanson JA. 2012. Inducible renitence limits Listeria monocytogenes escape from vacuoles in macrophages. J Immunol 189(9):4488-95. [PubMed: 23002437]  [MGI Ref ID J:190625]

Desai MS; Mariscalco MM; Tawil A; Vallejo JG; Smith CW. 2008. Atherogenic diet-induced hepatitis is partially dependent on murine TLR4. J Leukoc Biol 83(6):1336-44. [PubMed: 18334542]  [MGI Ref ID J:136848]

Diehl SA; McElvany B; Noubade R; Seeberger N; Harding B; Spach K; Teuscher C. 2014. G proteins Galphai1/3 are critical targets for Bordetella pertussis toxin-induced vasoactive amine sensitization. Infect Immun 82(2):773-82. [PubMed: 24478091]  [MGI Ref ID J:209809]

Dong B; Qi D; Yang L; Huang Y; Xiao X; Tai N; Wen L; Wong FS. 2012. TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes. Am J Physiol Heart Circ Physiol 303(6):H732-42. [PubMed: 22842069]  [MGI Ref ID J:191323]

Dvoriantchikova G; Barakat DJ; Hernandez E; Shestopalov VI; Ivanov D. 2010. Toll-like receptor 4 contributes to retinal ischemia/reperfusion injury. Mol Vis 16:1907-12. [PubMed: 21031135]  [MGI Ref ID J:167913]

Ehl S; Bischoff R; Ostler T; Vallbracht S; Schulte-Monting J; Poltorak A; Freudenberg M. 2004. The role of Toll-like receptor 4 versus interleukin-12 in immunity to respiratory syncytial virus. Eur J Immunol 34(4):1146-53. [PubMed: 15048726]  [MGI Ref ID J:88878]

Espinassous Q; Garcia-de-Paco E; Garcia-Verdugo I; Synguelakis M; von Aulock S; Sallenave JM; McKenzie AN; Kanellopoulos J. 2009. IL-33 enhances lipopolysaccharide-induced inflammatory cytokine production from mouse macrophages by regulating lipopolysaccharide receptor complex. J Immunol 183(2):1446-55. [PubMed: 19553541]  [MGI Ref ID J:151399]

Fan W; Morinaga H; Kim JJ; Bae E; Spann NJ; Heinz S; Glass CK; Olefsky JM. 2010. FoxO1 regulates Tlr4 inflammatory pathway signalling in macrophages. EMBO J 29(24):4223-36. [PubMed: 21045807]  [MGI Ref ID J:167177]

Fejer G; Wegner MD; Gyory I; Cohen I; Engelhard P; Voronov E; Manke T; Ruzsics Z; Dolken L; Prazeres da Costa O; Branzk N; Huber M; Prasse A; Schneider R; Apte RN; Galanos C; Freudenberg MA. 2013. Nontransformed, GM-CSF-dependent macrophage lines are a unique model to study tissue macrophage functions. Proc Natl Acad Sci U S A 110(24):E2191-8. [PubMed: 23708119]  [MGI Ref ID J:197404]

Fellner L; Irschick R; Schanda K; Reindl M; Klimaschewski L; Poewe W; Wenning GK; Stefanova N. 2013. Toll-like receptor 4 is required for alpha-synuclein dependent activation of microglia and astroglia. Glia 61(3):349-60. [PubMed: 23108585]  [MGI Ref ID J:191118]

Feng X; Deng T; Zhang Y; Su S; Wei C; Han D. 2011. Lipopolysaccharide inhibits macrophage phagocytosis of apoptotic neutrophils by regulating the production of tumour necrosis factor alpha and growth arrest-specific gene 6. Immunology 132(2):287-95. [PubMed: 21039473]  [MGI Ref ID J:168633]

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Rosen GD; Azoulay NG; Griffin EG; Newbury A; Koganti L; Fujisaki N; Takahashi E; Grant PE; Truong DT; Fitch RH; Lu L; Williams RW. 2012. Bilateral Subcortical Heterotopia with Partial Callosal Agenesis in a Mouse Mutant. Cereb Cortex :. [PubMed: 22455839]  [MGI Ref ID J:184128]

Rumbaut RE; Bellera RV; Randhawa JK; Shrimpton CN; Dasgupta SK; Dong JF; Burns AR. 2006. Endotoxin enhances microvascular thrombosis in mouse cremaster venules via a TLR4-dependent, neutrophil-independent mechanism. Am J Physiol Heart Circ Physiol 290(4):H1671-9. [PubMed: 16284241]  [MGI Ref ID J:108441]

Saberi M; Woods NB; de Luca C; Schenk S; Lu JC; Bandyopadhyay G; Verma IM; Olefsky JM. 2009. Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat-fed mice. Cell Metab 10(5):419-29. [PubMed: 19883619]  [MGI Ref ID J:155431]

Schmidt M; Raghavan B; Muller V; Vogl T; Fejer G; Tchaptchet S; Keck S; Kalis C; Nielsen PJ; Galanos C; Roth J; Skerra A; Martin SF; Freudenberg MA; Goebeler M. 2010. Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. Nat Immunol 11(9):814-9. [PubMed: 20711192]  [MGI Ref ID J:163916]

Schulthess FT ; Paroni F ; Sauter NS ; Shu L ; Ribaux P ; Haataja L ; Strieter RM ; Oberholzer J ; King CC ; Maedler K. 2009. CXCL10 impairs beta cell function and viability in diabetes through TLR4 signaling. Cell Metab 9(2):125-39. [PubMed: 19187771]  [MGI Ref ID J:146651]

Scott MJ; Billiar TR. 2008. Beta2-integrin-induced p38 MAPK activation is a key mediator in the CD14/TLR4/MD2-dependent uptake of lipopolysaccharide by hepatocytes. J Biol Chem 283(43):29433-46. [PubMed: 18701460]  [MGI Ref ID J:142561]

Seimon TA; Nadolski MJ; Liao X; Magallon J; Nguyen M; Feric NT; Koschinsky ML; Harkewicz R; Witztum JL; Tsimikas S; Golenbock D; Moore KJ; Tabas I. 2010. Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell Metab 12(5):467-82. [PubMed: 21035758]  [MGI Ref ID J:167910]

Seimon TA; Obstfeld A; Moore KJ; Golenbock DT; Tabas I. 2006. Combinatorial pattern recognition receptor signaling alters the balance of life and death in macrophages. Proc Natl Acad Sci U S A 103(52):19794-9. [PubMed: 17167049]  [MGI Ref ID J:118240]

Shakya AK; Kumar A; Klaczkowska D; Hultqvist M; Hagenow K; Holmdahl R; Nandakumar KS. 2011. Collagen Type II and a Thermo-Responsive Polymer of N-Isopropylacrylamide Induce Arthritis Independent of Toll-Like Receptors A Strong Influence by Major Histocompatibility Complex Class II and Ncf1 Genes. Am J Pathol 179(5):2490-500. [PubMed: 21933654]  [MGI Ref ID J:177359]

Shao B; Lu M; Katz SC; Varley AW; Hardwick J; Rogers TE; Ojogun N; Rockey DC; Dematteo RP; Munford RS. 2007. A host lipase detoxifies bacterial lipopolysaccharides in the liver and spleen. J Biol Chem 282(18):13726-35. [PubMed: 17322564]  [MGI Ref ID J:121874]

Shechter R; Ronen A; Rolls A; London A; Bakalash S; Young MJ; Schwartz M. 2008. Toll-like receptor 4 restricts retinal progenitor cell proliferation. J Cell Biol 183(3):393-400. [PubMed: 18981228]  [MGI Ref ID J:141070]

Shen XD; Ke B; Zhai Y; Gao F; Busuttil RW; Cheng G; Kupiec-Weglinski JW. 2005. Toll-like receptor and heme oxygenase-1 signaling in hepatic ischemia/reperfusion injury. Am J Transplant 5(8):1793-800. [PubMed: 15996225]  [MGI Ref ID J:114368]

Shi X; Siggins RW; Stanford WL; Melvan JN; Basson MD; Zhang P. 2013. Toll-like receptor 4/stem cell antigen 1 signaling promotes hematopoietic precursor cell commitment to granulocyte development during the granulopoietic response to Escherichia coli bacteremia. Infect Immun 81(6):2197-205. [PubMed: 23545304]  [MGI Ref ID J:199520]

Simonaro CM; Ge Y; Eliyahu E; He X; Jepsen KJ; Schuchman EH. 2010. Involvement of the Toll-like receptor 4 pathway and use of TNF-alpha antagonists for treatment of the mucopolysaccharidoses. Proc Natl Acad Sci U S A 107(1):222-7. [PubMed: 20018674]  [MGI Ref ID J:156466]

Sing A; Roggenkamp A; Geiger AM; Heesemann J. 2002. Yersinia enterocolitica evasion of the host innate immune response by V antigen-induced IL-10 production of macrophages is abrogated in IL-10-deficient mice. J Immunol 168(3):1315-21. [PubMed: 11801671]  [MGI Ref ID J:127288]

So EY; Kim BS. 2009. Theiler's virus infection induces TLR3-dependent upregulation of TLR2 critical for proinflammatory cytokine production. Glia 57(11):1216-26. [PubMed: 19191335]  [MGI Ref ID J:156204]

Speer T; Rohrer L; Blyszczuk P; Shroff R; Kuschnerus K; Krankel N; Kania G; Zewinger S; Akhmedov A; Shi Y; Martin T; Perisa D; Winnik S; Muller MF; Sester U; Wernicke G; Jung A; Gutteck U; Eriksson U; Geisel J; Deanfield J; von Eckardstein A; Luscher TF;Fliser D; Bahlmann FH; Landmesser U. 2013. Abnormal High-Density Lipoprotein Induces Endothelial Dysfunction via Activation of Toll-like Receptor-2. Immunity 38(4):754-68. [PubMed: 23477738]  [MGI Ref ID J:196201]

St John AL; Abraham SN. 2009. Salmonella disrupts lymph node architecture by TLR4-mediated suppression of homeostatic chemokines. Nat Med 15(11):1259-65. [PubMed: 19855398]  [MGI Ref ID J:155766]

Stark RJ; Aghakasiri N; Rumbaut RE. 2012. Platelet-derived Toll-like receptor 4 (Tlr-4) is sufficient to promote microvascular thrombosis in endotoxemia. PLoS One 7(7):e41254. [PubMed: 22911769]  [MGI Ref ID J:189884]

Stefanova N; Fellner L; Reindl M; Masliah E; Poewe W; Wenning GK. 2011. Toll-Like Receptor 4 Promotes alpha-Synuclein Clearance and Survival of Nigral Dopaminergic Neurons. Am J Pathol 179(2):954-63. [PubMed: 21801874]  [MGI Ref ID J:174596]

Tagliabue A; McCoy JL; Herberman RB. 1978. Refractoriness to migration inhibitory factor of macrophages of LPS nonresponder mouse strains. J Immunol 121(4):1223-6. [PubMed: 359704]  [MGI Ref ID J:6043]

Tanga FY; Nutile-McMenemy N; Deleo JA. 2005. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci U S A 102(16):5856-61. [PubMed: 15809417]  [MGI Ref ID J:97819]

Tarallo V; Hirano Y; Gelfand BD; Dridi S; Kerur N; Kim Y; Cho WG; Kaneko H; Fowler BJ; Bogdanovich S; Albuquerque RJ; Hauswirth WW; Chiodo VA; Kugel JF; Goodrich JA; Ponicsan SL; Chaudhuri G; Murphy MP; Dunaief JL; Ambati BK; Ogura Y; Yoo JW; Lee DK; Provost P; Hinton DR; Nunez G; Baffi JZ; Kleinman ME; Ambati J. 2012. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell 149(4):847-59. [PubMed: 22541070]  [MGI Ref ID J:186198]

Tchaptchet S; Gumenscheimer M; Kalis C; Freudenberg N; Holscher C; Kirschning CJ; Lamers M; Galanos C; Freudenberg MA. 2012. TLR9-dependent and independent pathways drive activation of the immune system by Propionibacterium acnes. PLoS One 7(6):e39155. [PubMed: 22745710]  [MGI Ref ID J:187937]

Thomas JA; Tsen MF; White DJ; Horton JW. 2002. TLR4 inactivation and rBPI(21) block burn-induced myocardial contractile dysfunction. Am J Physiol Heart Circ Physiol 283(4):H1645-55. [PubMed: 12234819]  [MGI Ref ID J:108049]

Tsukumo DM; Carvalho-Filho MA; Carvalheira JB; Prada PO; Hirabara SM; Schenka AA; Araujo EP; Vassallo J; Curi R; Velloso LA; Saad MJ. 2007. Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 56(8):1986-98. [PubMed: 17519423]  [MGI Ref ID J:126488]

Van Hove CL; Maes T; Joos GF; Tournoy KG. 2007. Prolonged inhaled allergen exposure can induce persistent tolerance. Am J Respir Cell Mol Biol 36(5):573-84. [PubMed: 17218615]  [MGI Ref ID J:136611]

Viriyakosol S; Fierer J; Brown GD; Kirkland TN. 2005. Innate immunity to the pathogenic fungus Coccidioides posadasii is dependent on Toll-like receptor 2 and Dectin-1. Infect Immun 73(3):1553-60. [PubMed: 15731053]  [MGI Ref ID J:96684]

Vogel SN; Johnson D; Perera PY; Medvedev A; Lariviere L; Qureshi ST ; Malo D. 1999. Cutting edge: functional characterization of the effect of the C3H/HeJ defect in mice that lack an Lpsn gene: in vivo evidence for a dominant negative mutation. J Immunol 162(10):5666-70. [PubMed: 10229796]  [MGI Ref ID J:54987]

Wang X; Ha T; Liu L; Zou J; Zhang X; Kalbfleisch J; Gao X; Williams D; Li C. 2013. Increased expression of microRNA-146a decreases myocardial ischaemia/reperfusion injury. Cardiovasc Res 97(3):432-42. [PubMed: 23208587]  [MGI Ref ID J:210282]

Wang X; Moser C; Louboutin JP; Lysenko ES; Weiner DJ; Weiser JN; Wilson JM. 2002. Toll-like receptor 4 mediates innate immune responses to Haemophilus influenzae infection in mouse lung. J Immunol 168(2):810-5. [PubMed: 11777976]  [MGI Ref ID J:73739]

Wang X; Zhou S; Chi Y; Wen X; Hoellwarth J; He L; Liu F; Wu C; Dhesi S; Zhao J; Hu W; Su C. 2009. CD4(+)CD25(+) Treg induction by an HSP60-derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent. Eur J Immunol 39(11):3052-3065. [PubMed: 19882655]  [MGI Ref ID J:154162]

Watanabe S; Kumazawa Y; Inoue J. 2013. Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14. PLoS One 8(4):e60078. [PubMed: 23565187]  [MGI Ref ID J:199946]

Watts BA 3rd; George T; Good DW. 2013. Lumen LPS inhibits HCOFormula absorption in the medullary thick ascending limb through TLR4-PI3K-Akt-mTOR-dependent inhibition of basolateral Na+/H+ exchange. Am J Physiol Renal Physiol 305(4):F451-62. [PubMed: 23698118]  [MGI Ref ID J:200847]

Watts BA 3rd; George T; Sherwood ER; Good DW. 2011. Basolateral LPS inhibits NHE3 and HCOFormula absorption through TLR4/MyD88-dependent ERK activation in medullary thick ascending limb. Am J Physiol Cell Physiol 301(6):C1296-306. [PubMed: 21881005]  [MGI Ref ID J:178333]

Wu J; Yan Z; Schwartz DE; Yu J; Malik AB; Hu G. 2013. Activation of NLRP3 Inflammasome in Alveolar Macrophages Contributes to Mechanical Stretch-Induced Lung Inflammation and Injury. J Immunol 190(7):3590-9. [PubMed: 23436933]  [MGI Ref ID J:194745]

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Xu H; Su Z; Wu J; Yang M; Penninger JM; Martin CM; Kvietys PR; Rui T. 2010. The alarmin cytokine, high mobility group box 1, is produced by viable cardiomyocytes and mediates the lipopolysaccharide-induced myocardial dysfunction via a TLR4/phosphatidylinositol 3-kinase gamma pathway. J Immunol 184(3):1492-8. [PubMed: 20028656]  [MGI Ref ID J:159535]

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Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as homozygotes.
Mating SystemHomozygote x Homozygote         (Female x Male)   28-APR-09
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 $199.90Female or MaleHomozygous for Tlr4lps-del  
Price per Pair (US dollars $)Pair Genotype
$399.80Homozygous for Tlr4lps-del x Homozygous for Tlr4lps-del  

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 $259.90Female or MaleHomozygous for Tlr4lps-del  
Price per Pair (US dollars $)Pair Genotype
$519.80Homozygous for Tlr4lps-del x Homozygous for Tlr4lps-del  

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.

General Supply Notes

  • View the complete collection of spontaneous mutants in the Mouse Mutant Resource.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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General Terms and Conditions


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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.

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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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