Macrophages in these mice fail to produce tumor necrosis factor (TNF) upon challenge from synthetic lipid A, endotoxin lipopolysaccharide (LPS), and dsRNA. These mice may be useful in studies of immunodeficiency and host response to bacterial endotoxins and viruses.
Bruce Beutler, University of Texas Southwestern Medical
Mice that are homozygous for the mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This single base pair deletion mutation was induced by ENU mutagenesis. Unlike wildtype macrophages, macrophages derived from these animals fail to respond to synthetic lipid A, endotoxin lipopolysaccharide (LPS), and dsRNA with production of tumor necrosis factor (TNF). Macrophages are less susceptible to LPS-induced cytotoxicity. Nitrous oxide and type I interferon production in activated macrophages is impaired. Homozygotes exhibit increased susceptibility to mouse cytomegalovirus. Although homozygotes are resistant to challenges with LPS, the mice will become ill and some may die.
This strain was developed using ENU mutagenesis of male C57BL/6 mice. The founding male (#9324) was selected from the F3 generation using a screening protocol for macrophage response to lipid A and endotoxin lopopolyscaccharide (LPS). The ENU treatment induced a single base pair deletion at codon 708.
|Allele Name||lipopolysaccharide 2|
|Allele Type||Chemically induced (ENU) (Not Specified)|
|Allele Synonym(s)||lipopolysaccharide 2; Ticam1Lps2|
|Gene Symbol and Name||Ticam1, toll-like receptor adaptor molecule 1|
|Gene Synonym(s)||MyD88-3; AW547018; expressed sequence AW046014; TRIF; IIAE6; TICAM-1; PRVTIRB; expressed sequence AW547018; AW046014; Trif|
|Strain of Origin||C57BL/6J|
|Molecular Note||ENU mutagenesis induced the deletion of a single guanine within codon 708, resulting in a frameshift mutation. The mutation was predicted to replace 24 C-terminal residues with 11 unrelated residues. The mutation was initially detected by screening macrophages for their competence to respond to LPS.|
|Mutations Made By|| |
Bruce Beutler, University of Texas Southwestern Medical
This strain originated on a C57BL/6 background. Heterozygotes were intercrossed to generate homozygotes. SPF (Specific Pathogen Free) conditions should be implemented as these mice are immunodeficient.
When using the TrifLps2 mouse strain in a publication, please cite the originating article(s) and include JAX stock #005037 in your Materials and Methods section.
"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.