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Strain Name:

B6.129-Tlr2tm1Kir/J

Stock Number:

004650

Availability:

Level 4

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Additional Licensing and Use Restrictions

Genes & Alleles   Tlr2;   Tlr2tm1Kir;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Targeted Mutation
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Carsten Kirschning,   Technical University of Munich
GenerationN9+F11 (08-JAN-08)

Strain Description
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of isolated peritoneal macrophages. Bone marrow derived macrophages do not respond to spirochete (Borrelia burgdorferi) lipoprotein challenge, although non-lipoprotein sonicate stimulates activation. Arthritis due to B. burgdorferi infection, as assessed by rear ankle swelling, is more severe in mutant mice. Tissues of infected mutants can contain up to 100 times higher bacteria levels than those found in wildtype littermates. Elevated spirochete numbers persist 8 weeks post-infection. Homozygotes do not produce TNF-alpha or IL-6, and do not develop symptoms of illness when treated with leptospiral (Leptospira interrogans) lippolysaccharide (LPS). This mutant mouse strain may be useful in studies of host response to bacterial endotoxins such as septic shock.

Strain Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt sequence of the targeted gene encoding the C-terminus of the extracellular and part of the transmembrane domains. The construct was electroporated into 129/SvJ derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Mammalian Phenotype Terms assigned by genotype

Tlr2tm1Kir/Tlr2tm1Kir

        B6.Cg-Tlr2tm1Kir
  • immune system phenotype
  • abnormal macrophage physiology (MGI Ref ID J:85323)
    • bone marrow derived macrophages did not respond to spirochete (Borrelia burgdorferi) lipoprotien, though non-lipoprotein sonicate stimulated activation
    • normal Borelia specific Ab response, indicating unimpaired acquired host defense
  • increased susceptibility to bacterial infection (MGI Ref ID J:85323)
    • increased severity of arthritis due to B. burgdorferi infection
    • infected tissue contains up to 100x higher spirochete level than wild type
    • infection persists 8 weeks post-infection
    • no symptoms when treated leptospiral LPS
    • normal Borelia specific Ab response, indicating unimpaired acquired host defense

Tlr2tm1Kir/Tlr2tm1Kir

        B6.129-Tlr2tm1Kir
  • life span-post-weaning/aging
  • abnormal induced morbidity/mortality (MGI Ref ID J:121930)
    • mutants are protected from bacterial lipoteichoic acid exposure after priming by IFNG and sensitization with D-galactosamine, while Tlr4-deficient mice and wild-type are susceptible to lethal shock by this treatment
    • heat-inactivated E. coli exposure results in fatal toxemia however, similar to wild type mice heat-inactivated E. coli exposure results in fatal toxemia
  • immune system phenotype
  • abnormal cytokine secretion (MGI Ref ID J:121930)
    • systemic challenge with Pam3-CSK4, a bacterial lipopeptide analog, does not induce substantial secretion of Il6 or TNFalpha, compared to marked levels produced in wild-type mice
    • decreased interleukin-1 beta secretion (MGI Ref ID J:129871)
      • IL1-beta secretion by peritoneal macrophages is reduced by 50% in response to Listeria infection
      • peritoneal macrophages fail to secrete IL-1beta in response to a TLR2 agonist
    • decreased interleukin-6 secretion (MGI Ref ID J:129871)
      • IL-6 secretion by peritoneal macrophages is reduced by 8-fold in response to Listeria infection
      • peritoneal macrophages fail to secrete IL6 in response to a TLR2 agonist
    • decreased tumor necrosis factor secretion (MGI Ref ID J:129871)
      • TNF secretion by peritoneal macrophages is reduced by 50% in response to Listeria infection
  • decreased susceptibility to bacterial infection (MGI Ref ID J:121930)
    • mice are resistant to lethal-shock syndrome induced by B. subtilis challenge, whereas wild-type and Tlr4-deficient mice are
    • susceptibilities to L. monocytogenes and S. aureus challenge are not different from wild-type mice
  • cellular phenotype
  • decreased cell proliferation (MGI Ref ID J:121930)
    • splenocytes do not proliferate in response to bacterial peptidoglycan or lipoteichoic acid, but do respond normally with proliferation to enterobacterial LPS

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Tlr2tm1Kir/Tlr2tm1Kir

        Background Not Specified
  • life span-post-weaning/aging
  • abnormal induced morbidity/mortality (MGI Ref ID J:96018)
    • homozygous null mice succumbed to S. aureus infection within 5 days
  • immune system phenotype
  • abnormal macrophage physiology (MGI Ref ID J:96018)
    • peritoneal macrophages were completely unresponsive and produced little or no TNF when stimulated with lipoteichoic acid (LTA) or macrophage-activating lipopeptide 2 (MALP-2) from Mycoplasma pneumoniae
  • increased susceptibility to bacterial infection (MGI Ref ID J:96018)
    • during a 7-dap period, homozygous null mice were permissive for the growth of intradermally inoculated S. aureus, whereas the bacteria were cleared from wildtype

Gene & Allele Details

Allele Symbol Tlr2tm1Kir
Allele Name targeted mutation 1, Carsten J Kirschning
Common Name(s) Ly105; TLR2-;
Mutation Made By Carsten Kirschning,   Technical University of Munich
Strain of Origin129
Gene Symbol and Name Tlr2, toll-like receptor 2
Chromosome 3
Gene Common Name(s) CD282; Ly105; TIL4;
Molecular Note C-terminal sequence encoding the extracellular domain and a portion of the transmembrane domain was replaced with a neo cassette inserted by homologous recombination. Protein was undetected by Western blot analysis of peritoneal macrophages obtained fromhomozygous mutant mice. [MGI Ref ID J:85323]

Control Information

  Allele   Control
 Tlr2tm1Kir  000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Tlr2tm1Kir, tm1Dgen

Colony Maintenance

Breeding & HusbandryHeterozygotes were intercrossed, and then backcrossed to C57BL/6J for 9 generations. The strain is maintained as a homozygote. Expected coat color is black non-agouti.
Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying other alleles of Tlr2
005846   B6.129S1-Tlr2tm1Dgen/J
View Strains carrying other alleles of Tlr2     (1 strain)

Additional Web Information

Congenic Nomenclature
JAX Notes, Summer 2005; 498. Toll-like Receptor JAX® Mice for Immunological Research.

Animal Health Reports

Room Number           AX29

Research Applications

This mouse can be used to support research in many areas including:

Tlr2tm1Kir related

Cell Biology Research
Signal Transduction

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers (Tlr deficiency)
CD Antigens, Antigen Receptors, and Histocompatibility Markers (genes regulating susceptibility to infectious disease and endotoxin)
Immunodeficiency (Tlr deficiency)
Immunodeficiency Associated with Other Defects

References

Selected Reference(s)

Wooten RM; Ma Y; Yoder RA; Brown JP; Weis JH; Zachary JF; Kirschning CJ; Weis JJ. 2002. Toll-like receptor 2 is required for innate, but not acquired, host defense to Borrelia burgdorferi. J Immunol 168(1):348-55. [PubMed: 11751980]  [MGI Ref ID J:85323]

Additional References

Price and Supply Information

Strain Name: B6.129-Tlr2tm1Kir/J
Stock Number: 004650

Price Details

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Supply Details

Standard SupplyLevel 4. Up to 10 mice. Larger quantities or custom orders arranged upon request. Expected delivery up to one to three months.
Supply Notes Shipped at a specific age in weeks. Mice at a precise age in days, littermates and retired breeders are also available.
Strains that must be genotyped are not available until five to seven weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

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For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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