Type Congenic; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote (Female x Male) 28-APR-09 Species laboratory mouse Background Strain C57BL/6 Donor Strain C57BL/10ScN H2 Haplotype b Generation N6+N1F7 (24-MAR-11)
Generation DefinitionsAppearance
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Related Genotype: a/aDescription
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 has a 7 kb deletion in the Tlr4 gene that results in absence of both mRNA and protein and thus exhibits 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 | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Strains carrying Tlr4lps-del allele
003752 C57BL/10ScNJ View Strains carrying Tlr4lps-del (1 strain)
Strains carrying other alleles of Tlr4
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 (7 strains)
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. Colorectal Cancer; CRC (TLR4)
Macular Degeneration, Age-Related, 10; ARMD10 (TLR4)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
The following phenotype information may relate to a genetic background differing from 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
- 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
- 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)
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
- abnormal retinal progenitor cell morphology
- abnormal retinal rod bipolar cell morphology
- nervous system phenotype
- abnormal retinal rod bipolar cell morphology
- abnormal retinal rod cell morphology
- 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)
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
- 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
- abnormal neuron differentiation
- cellular phenotype
- abnormal neuron differentiation
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Tlr4lps-del relatedImmunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Tlr deficiency
Immunodeficiency
Tlr deficiency
Inflammation
Tlr deficiency
Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Tlr deficiency
Immunodeficiency
Tlr deficiency
Inflammation
Tlr deficiency
| Allele Symbol | Tlr4lps-del | ||
|---|---|---|---|
| Allele Name | defective lipopolysaccharide response, deletion | ||
| Allele Type | Spontaneous | ||
| Common Name(s) | TLR4-KO; TLR4lps-; Tlr4-; | ||
| Strain of Origin | C57BL/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 Protocols
Tlr4lps-del, Melt Curve Analysis
Tlr4lps-del, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
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Henao-Mejia J; Elinav E; Jin C; Hao L; Mehal WZ; Strowig T; Thaiss CA; Kau AL; Eisenbarth SC; Jurczak MJ; Camporez JP; Shulman GI; Gordon JI; Hoffman HM; Flavell RA. 2012. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482(7384):179-85. [PubMed: 22297845] [MGI Ref ID J:181354]
Hua F; Ha T; Ma J; Li Y; Kelley J; Gao X; Browder IW; Kao RL; Williams DL; Li C. 2007. Protection against myocardial ischemia/reperfusion injury in TLR4-deficient mice is mediated through a phosphoinositide 3-kinase-dependent mechanism. J Immunol 178(11):7317-24. [PubMed: 17513782] [MGI Ref ID J:147828]
Hua F; Ma J; Ha T; Kelley JL; Kao RL; Schweitzer JB; Kalbfleisch JH; Williams DL; Li C. 2009. Differential roles of TLR2 and TLR4 in acute focal cerebral ischemia/reperfusion injury in mice. Brain Res 1262:100-8. [PubMed: 19401158] [MGI Ref ID J:148091]
Hua F; Ma J; Ha T; Xia Y; Kelley J; Williams DL; Kao RL; Browder IW; Schweitzer JB; Kalbfleisch JH; Li C. 2007. Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. J Neuroimmunol 190(1-2):101-11. [PubMed: 17884182] [MGI Ref ID J:129001]
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Jayachandran M; Brunn GJ; Karnicki K; Miller RS; Owen WG; Miller VM. 2007. In vivo effects of lipopolysaccharide and TLR4 on platelet production and activity: implications for thrombotic risk. J Appl Physiol 102(1):429-33. [PubMed: 16916914] [MGI Ref ID J:135961]
John B; Crispe IN. 2005. TLR-4 regulates CD8+ T cell trapping in the liver. J Immunol 175(3):1643-50. [PubMed: 16034104] [MGI Ref ID J:107284]
Johnson GB; Riggs BL; Platt JL. 2004. A genetic basis for the 'Adonis' phenotype of low adiposity and strong bones. FASEB J 18(11):1282-4. [PubMed: 15208271] [MGI Ref ID J:118467]
Joosten LA; Koenders MI; Smeets RL; Heuvelmans-Jacobs M; Helsen MM; Takeda K; Akira S; Lubberts E; van de Loo FA; van den Berg WB. 2003. Toll-like receptor 2 pathway drives streptococcal cell wall-induced joint inflammation: critical role of myeloid differentiation factor 88. J Immunol 171(11):6145-53. [PubMed: 14634130] [MGI Ref ID J:119063]
Jung ID; Jeong SK; Lee CM; Noh KT; Heo DR; Shin YK; Yun CH; Koh WJ; Akira S; Whang J; Kim HJ; Park WS; Shin SJ; Park YM. 2011. Enhanced Efficacy of Therapeutic Cancer Vaccines Produced by Co-Treatment with Mycobacterium tuberculosis Heparin-Binding Hemagglutinin, a Novel TLR4 Agonist. Cancer Res 71(8):2858-2870. [PubMed: 21368092] [MGI Ref ID J:170995]
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Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as homozygotes. Mating System Homozygote x Homozygote (Female x Male) 28-APR-09 Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
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Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $177.00 Female or Male Homozygous for Tlr4lps-del
Price per Pair (US dollars $) Pair Genotype $354.00 Homozygous for Tlr4lps-del x Homozygous for Tlr4lps-del Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $230.10 Female or Male Homozygous for Tlr4lps-del
Price per Pair (US dollars $) Pair Genotype $460.20 Homozygous for Tlr4lps-del x Homozygous for Tlr4lps-del Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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