immunoblot analysis of lysates of heterozygous mutant mouse embryonic fibroblasts (MEFs) using antibody to IkappaB demonstrates normal degradation by these cells of IkappaB in response to interleukin 1 (IL-1)
peritoneal macrophages from homozygous mice secrete normal amounts of type 1 interferon in response to polyI:C, a TLR3-activating ligand
peritoneal macrophages from homozygous mice secrete nearly normal amounts of type 1 interferon in response to the diacyl peptides MALP-2 and PAM2CSK4, which induce signaling via TLR2 or the TLR2/TLR6 heterodimer
peritoneal macrophages from homozygous mice normally phosphorylate c-JUN, N-terminal kinase, extracellular signal-regulated kinase, p38, and IkappaB in response to MALP-2 and PAM2CSK4, diacyl peptides that signal via the TLR2/TLR6 heterodimer or TLR2
following injection with MALP-2, a diacyl lipopeptide that signals via the TLR2/TLR6 heterodimer or TLR2, homozygous mice all died within 12 hours, similarly to wild-type mice, which were all dead within 16 hours
abnormal immune system physiology (MGI Ref ID J:110094)
immunoblot analysis of lysates of homozygous mutant mouse embryonic fibroblasts (MEFs) using antibody to IkappaB demonstrates failure of these cells to degrade IkappaB in response to interleukin 1 (IL-1)
abnormal macrophage physiology (MGI Ref ID J:110094)
peritoneal macrophages from homozygous mice exhibit no type 1 interferon secretion in response to lipopolysaccharide (LPS), a TLR4-activating ligand, at low doses and a markedly diminished response to LPS at high doses
peritoneal macrophages from homozygous mice fail to secrete type 1 interferon in response to the TLR1/TLR2-activating lipopepti de PAM3CSK4
peritoneal macrophages from homozygous mice fail to secrete type 1 interferon in response to the TLR2/TLR6-activating ligand lipoteichoic acid
peritoneal macrophages from homozygous mice fail to secrete type 1 interferon in response to resiquimod, a TLR7-activating ligand
peritoneal macrophages from homozygous mice fail to secrete type 1 interferon in response to unmethylated CpG DNA, a TLR9-activating ligand
immunoblot analysis of lysates of homozygous mutant peritoneal macrophages using antibodies to phosphorylated proteins demonstrates failure of these cells to phosphorylate/activate Ikappa B, JUN N-terminal kinase (JNK) or extracellular signal-related kinase (ERK) in response to the TLR7-activating ligand resiquimod
homozygous mutant peritoneal macrophages fail to phosphorylate/activate Ikappa B, JUN N-terminal kinase (JNK) or extracellular signal-related kinase (ERK) in response to the TLR1/TLR2-activating lipopeptide PAM3CSK4
increased susceptibility to bacterial infection (MGI Ref ID J:110094)
inocula of Listeria monocytogenes that are easily controlled by wild-type mice are lethal to homozygous mutants
intradermally inoculated luminescent Streptococcus pyogenes, which are rapidly contained, then cleared by wild-type mice, are able to proliferate in homozygous mutant mice before the infection eventually is controlled
increased susceptibility to viral infection (MGI Ref ID J:110094)
inocula of mouse cytomegalovirus (CMV) that are easily controlled by wild-type mice are lethal to homozygous mutants
Founder genetic background: C57BL/6J
Strain genetic background: C57BL/6J
Strain Development: Homozygous mutant was picked up by the screening, and backcrossed to its parents,
after that homozygotes were kept by sib-mating.
Suggested Control Mice:
Immunology and Inflammation
Bruce Beutler, M.D., The Scripps Research Institute
Jiang Z; Georgel P; Li C; Choe J; Crozat K; Rutschmann S; Du X; Bigby T; Mudd S; Sovath S; Wilson IA; Olson A; Beutler B, Details of Toll-like receptor:adapter interaction revealed by germ-line mutagenesis., Proc Natl Acad Sci U S A 2006 Jul 18;103(29):10961-6
(Medline PMID: 16832055)
Croker BA; Lawson BR; Berger M; Eidenschenk C; Blasius AL; Moresco EM; Sovath S; Cengia L; Shultz LD; Theofilopoulos AN; Pettersson S; Beutler BA, Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger., Proc Natl Acad Sci U S A 2008 Sep 30;105(39):15028-33
(Medline PMID: 18806225)
For additional information see: Mutagenetix, a catalog of mutations identified in the Beutler Laboratory at The Scripps Research Institute.
Health Status Report
Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email firstname.lastname@example.org.
Order Request Information
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Conditions of Distribution:
Distribution of this strain requires submission of the MMRRC Conditions of Use (COU).
A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded
to your institutional official for completion.
The donor or their institution limits the distribution to non-profit institutions only.
Additional charges may apply for any special requests. Shipping
costs are in addition to the basic distribution/resuscitation
fees. Information on shipping costs and any additional charges will be provided
by the supplying MMRRC facility.
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(Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item #
Fee/unit (US $)
Litter recovered from cryo-archive
Recovered litter1; additional fees for any special requests.
Approximate quantity3: 20-40 embryos / aliquot
The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.
An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.
An aliquot contains a sufficient number of embryos (in one or more
vials and based on the transfer success rate of the MMRRC facility) to
transfer to at least two recipients. The MMRRC makes no guarantee concerning
embryo transfer success experienced in the recipient investigator's laboratory.
Neither gender nor genotype ratios are guaranteed.
To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the "Request this Strain" button above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.
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