Strain Detail Sheet

Phenotype:
Homozygous phenotype: Macrophages show no response to TLR2/6 ligands

Heterozygous phenotype: Normal as wild type

Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

Tlr6^int/Tlr6^int

        C57BL/6-Tlr6<int>

• immune system phenotype
  • abnormal adaptive immunity (MGI Ref ID J:110094)
    • abnormal macrophage physiology (MGI Ref ID J:110094)
      • peritoneal macrophages from homozygous mice fail to secrete type 1 interferon in response to peptidoglycan, lipoteichoic acid or MALP-2, all of which induce signaling via the TLR2/TLR6 heterodimeer
      • peritoneal macrophages from homozygous mice exhibit a partial type 1 interferon secretory response to PAM2CSK4 in a TLR2-dependent manner
      • immunoblot analysis of lysates of homozygous mutant peritoneal macrophages using antibodies to phosphorylated proteins demonstrates failure of these cells to phosphorylate/activate IkappaB, JUN N-terminal kinase (JNK) or extracellular signal-related kinase (ERK) in response to MALP-2, a diacyl peptide that induces signaling TLR2 or the TLR2/TLR6 heterodimer
  • abnormal cell-mediated immunity (MGI Ref ID J:110094)
    • abnormal macrophage physiology (MGI Ref ID J:110094)
      • peritoneal macrophages from homozygous mice fail to secrete type 1 interferon in response to peptidoglycan, lipoteichoic acid or MALP-2, all of which induce signaling via the TLR2/TLR6 heterodimeer
      • peritoneal macrophages from homozygous mice exhibit a partial type 1 interferon secretory response to PAM2CSK4 in a TLR2-dependent manner
      • immunoblot analysis of lysates of homozygous mutant peritoneal macrophages using antibodies to phosphorylated proteins demonstrates failure of these cells to phosphorylate/activate IkappaB, JUN N-terminal kinase (JNK) or extracellular signal-related kinase (ERK) in response to MALP-2, a diacyl peptide that induces signaling TLR2 or the TLR2/TLR6 heterodimer
  • abnormal innate immunity (MGI Ref ID J:110094)
    • abnormal macrophage physiology (MGI Ref ID J:110094)
      • peritoneal macrophages from homozygous mice fail to secrete type 1 interferon in response to peptidogl ycan, lipoteichoic acid or MALP-2, all of which induce signaling via the TLR2/TLR6 heterodimeer
      • peritoneal macrophages from homozygous mice exhibit a partial type 1 interferon secretory response to PAM2CSK4 in a TLR2-dependent manner
      • immunoblot analysis of lysates of homozygous mutant peritoneal macrophages using antibodies to phosphorylated proteins demonstrates failure of these cells to phosphorylate/activate IkappaB, JUN N-terminal kinase (JNK) or extracellular signal-related kinase (ERK) in response to MALP-2, a diacyl peptide that induces signaling TLR2 or the TLR2/TLR6 heterodimer

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.

Donor: Bruce Beutler, M.D., The Scripps Research Institute

Primary Reference:

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)

For additional information see: Mutagenetix, a catalog of mutations identified in the Beutler Laboratory at The Scripps Research Institute.

None

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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MMRRC Item # Description	Distribution Fee/unit (US $)	Units	Notes
010474-UCD-RESUS Litter recovered from cryo-archive	$2,022.00 Non-Profit	Litter	Recovered litter1; additional fees for any special requests.
010474-UCD-SPERM Cryo-preserved spermatozoa	$437.00 Non-Profit	Aliquot	Approximate quantity.2
010474-UCD-EMBRYO Cryo-preserved embryos	$1,038.00 Non-Profit	Aliquot	Approximate quantity3: 20-40 embryos / aliquot

¹ 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 breedable 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.

² An aliquot contains sufficient material (volume and concentration) for at least two IVF or several artificial inseminations (based on our procedures). The MMRRC makes no guarantee concerning success of these procedures when performed outside the MMRRC facilities.

³ 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.