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.Read More +
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).
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.
|Allele Name||defective lipopolysaccharide response, deletion|
|Allele Synonym(s)||TLR4-KO; TLR4lps-; Tlr4-|
|Gene Symbol and Name||Tlr4, toll-like receptor 4|
|Gene Synonym(s)||ARMD10; CD284; Lps; Lps; RAS-like, family 2, locus 8; Rasl2-8; Rasl2-8; TLR-4; TOLL; lipopolysaccharide response; lipopolysaccharide response|
|Strain of Origin||C57BL/10ScN|
|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.|
When maintaining a live colony, these mice are bred as homozygotes.
When using the B6.B10ScN-Tlr4lps-del/JthJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #007227 in your Materials and Methods section.
|Heterozygous for Tlr4<lps-del>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
"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"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "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 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, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
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, PRODUCTS or SERVICES 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.