Strain Name:

B6;129S1-Tiraptm1Medz/J

Stock Number:

017629

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Tirap homozygous mutant mice show defects in cytokine production and in activation of nuclear factor NF-κB and mitogen-activated protein kinases in response to lipopolysaccharide and to bacterial lipoprotein. These mice may be useful in studies of the toll-like receptor pathway involvement in innate and adaptive immune responses.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation+pN1
Generation Definitions
 
Donating InvestigatorDr. Ruslan Medzhitov,   Yale School of Medicine

Description
Tirap (toll-interleukin 1 receptor (TIR) domain-containing adaptor protein), is a component of the toll-like receptor (TLR) signaling pathway that is associated with both innate and adaptive immune responses.

TIRAP-deficient mice respond normally to TLR5, TLR7, and TLR9 ligands, as well as to IL-1 and IL-18, but have defects in cytokine production and in activation of nuclear factor NF-κB and mitogen-activated protein kinases in response to lipopolysaccharide (a ligand of TLR4) and to bacterial lipoprotein (a ligand of TLR2). Homozygous Tirap mutant mice are born at expected Mendelian ratios and show no obvious gross abnormalities. A lack of expression has been confirmed in the spleen and macrophages.

Development
A 640 bp exon encoding most of the coding sequence of the gene was replaced with a neomycin resistance cassette. 129S1/Sv-Oca2+Tyr+Kitl +-derived W9.5 embryonic stem (ES) cells were used to create the mutation. This strain was backcrossed two times to C57BL/6 by the donating laboratory.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Bacteremia, Susceptibility to, 1; BACTS1   (TIRAP)
Invasive Pneumococcal Disease, Recurrent Isolated, 1; IPD1   (TIRAP)
Malaria, Susceptibility to   (TIRAP)
Mycobacterium Tuberculosis, Susceptibility to   (TIRAP)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Tiraptm1Medz/Tiraptm1Medz

        involves: 129S1/Sv * C57BL/6
  • immune system phenotype
  • abnormal dendritic cell physiology
    • production of IL-6, IL-12 and TNF-alpha by dendritic cells was significantly reduced in response to LPS and BLP, but not CpG or R-848, however dendritic cells were able to mature in response to LPS and CpG   (MGI Ref ID J:96773)
    • dendritic cells stimulated with LPS activated NF-kappaB with delayed kinetics   (MGI Ref ID J:96773)
  • abnormal macrophage physiology
    • production of IL-6, IL-12 and TNF-alpha by bone marrow derived macrophages was significantly reduced in response to LPS and BLP, but not CpG   (MGI Ref ID J:96773)
    • activation of NF-kappaB, JNK, p38 and ERK in bone marrow derived macrophages was delayed in response to LPS and BLP but not CpG   (MGI Ref ID J:96773)
  • decreased B cell proliferation
    • splenocytes showed a defect in proliferation in response to the TLR4 ligand lipopolysaccharide (LPS) and ligand bacterial lipopeptide (BLP) that signals through the TLR1-TLR2 heterodimer but not to the TLR9 ligand unmethylated CpG DNA (CpG) or to the TLR7 ligand resiquimod (R-848)   (MGI Ref ID J:96773)
  • hematopoietic system phenotype
  • abnormal macrophage physiology
    • production of IL-6, IL-12 and TNF-alpha by bone marrow derived macrophages was significantly reduced in response to LPS and BLP, but not CpG   (MGI Ref ID J:96773)
    • activation of NF-kappaB, JNK, p38 and ERK in bone marrow derived macrophages was delayed in response to LPS and BLP but not CpG   (MGI Ref ID J:96773)
  • decreased B cell proliferation
    • splenocytes showed a defect in proliferation in response to the TLR4 ligand lipopolysaccharide (LPS) and ligand bacterial lipopeptide (BLP) that signals through the TLR1-TLR2 heterodimer but not to the TLR9 ligand unmethylated CpG DNA (CpG) or to the TLR7 ligand resiquimod (R-848)   (MGI Ref ID J:96773)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Tiraptm1Medz/Tiraptm1Medz

        involves: 129S1/Sv
  • mortality/aging
  • increased sensitivity to induced morbidity/mortality
    • died more frequently than wildtype after S. aureus infection   (MGI Ref ID J:96018)
  • immune system phenotype
  • abnormal macrophage physiology
    • peritoneal macrophages showed only a residual response with a reduction of TNF production when stimulated with lipoteichoic acid (LTA) or macrophage-activating lipopeptide 2 (MALP-2) from Mycoplasma pneumoniae   (MGI Ref ID J:96018)
  • increased susceptibility to bacterial infection
    • increased susceptibility to S. aureus infection   (MGI Ref ID J:96018)
  • cardiovascular system phenotype
  • altered response to myocardial infarction
    • improved recovery of left ventricular function during reperfusion following ischemia   (MGI Ref ID J:119941)
  • homeostasis/metabolism phenotype
  • altered response to myocardial infarction
    • improved recovery of left ventricular function during reperfusion following ischemia   (MGI Ref ID J:119941)
  • hematopoietic system phenotype
  • abnormal macrophage physiology
    • peritoneal macrophages showed only a residual response with a reduction of TNF production when stimulated with lipoteichoic acid (LTA) or macrophage-activating lipopeptide 2 (MALP-2) from Mycoplasma pneumoniae   (MGI Ref ID J:96018)
View Research Applications

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

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Growth Factors/Receptors/Cytokines

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tiraptm1Medz
Allele Name targeted mutation 1, Ruslan Medzhltov
Allele Type Targeted (Null/Knockout)
Common Name(s) TIRAPtm1MD; Tirap-;
Mutation Made ByDr. Ruslan Medzhitov,   Yale School of Medicine
Strain of Origin129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name Tirap, toll-interleukin 1 receptor (TIR) domain-containing adaptor protein
Chromosome 9
Gene Common Name(s) AA407980; BACTS1; C130027E04Rik; Mal; MyD88-2; MyD88-adapter-like; RIKEN cDNA C130027E04 gene; expressed sequence AA407980; wyatt;
Molecular Note A neomycin resistance cassette replaced a 640 bp exon encoding most of the coding sequence. RT-PCR of mutant mice confirmed absence of transcript. [MGI Ref ID J:96773]

Genotyping

Genotyping Information

Genotyping Protocols

Tiraptm1Medzalternate1, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Tiraptm1Medz related

Bonilla DL; Bhattacharya A; Sha Y; Xu Y; Xiang Q; Kan A; Jagannath C; Komatsu M; Eissa NT. 2013. Autophagy regulates phagocytosis by modulating the expression of scavenger receptors. Immunity 39(3):537-47. [PubMed: 24035364]  [MGI Ref ID J:208209]

Ding A; Yu H; Yang J; Shi S; Ehrt S. 2005. Induction of macrophage-derived SLPI by Mycobacterium tuberculosis depends on TLR2 but not MyD88. Immunology 116(3):381-9. [PubMed: 16236128]  [MGI Ref ID J:103462]

Dong JW; Vallejo JG; Tzeng HP; Thomas JA; Mann DL. 2010. Innate immunity mediates myocardial preconditioning through Toll-like receptor 2 and TIRAP-dependent signaling pathways. Am J Physiol Heart Circ Physiol 298(3):H1079-87. [PubMed: 20061547]  [MGI Ref ID J:158423]

Doz E; Rose S; Nigou J; Gilleron M; Puzo G; Erard F; Ryffel B; Quesniaux VF. 2007. Acylation Determines the Toll-like receptor (TLR)-dependent Positive Versus TLR2-, Mannose Receptor-, and SIGNR1-independent Negative Regulation of Pro-inflammatory Cytokines by Mycobacterial Lipomannan. J Biol Chem 282(36):26014-26025. [PubMed: 17617634]  [MGI Ref ID J:124650]

Fremond CM; Togbe D; Doz E; Rose S; Vasseur V; Maillet I; Jacobs M; Ryffel B; Quesniaux VF. 2007. IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection. J Immunol 179(2):1178-89. [PubMed: 17617611]  [MGI Ref ID J:149392]

Gandhi A; Guo T; Shah P; Moorthy B; Ghose R. 2013. Chlorpromazine-induced hepatotoxicity during inflammation is mediated by TIRAP-dependent signaling pathway in mice. Toxicol Appl Pharmacol 266(3):430-8. [PubMed: 23238562]  [MGI Ref ID J:193330]

Georgel P; Jiang Z; Kunz S; Janssen E; Mols J; Hoebe K; Bahram S; Oldstone MB; Beutler B. 2007. Vesicular stomatitis virus glycoprotein G activates a specific antiviral Toll-like receptor 4-dependent pathway. Virology 362(2):304-13. [PubMed: 17292937]  [MGI Ref ID J:124488]

Hoebe K; Georgel P; Rutschmann S; Du X; Mudd S; Crozat K; Sovath S; Shamel L; Hartung T; Zahringer U; Beutler B. 2005. CD36 is a sensor of diacylglycerides. Nature 433(7025):523-7. [PubMed: 15690042]  [MGI Ref ID J:96018]

Horng T; Barton GM; Flavell RA; Medzhitov R. 2002. The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 420(6913):329-33. [PubMed: 12447442]  [MGI Ref ID J:96773]

Leal SM Jr; Cowden S; Hsia YC; Ghannoum MA; Momany M; Pearlman E. 2010. Distinct roles for Dectin-1 and TLR4 in the pathogenesis of Aspergillus fumigatus keratitis. PLoS Pathog 6:e1000976. [PubMed: 20617171]  [MGI Ref ID J:162398]

Lebeis SL; Bommarius B; Parkos CA; Sherman MA; Kalman D. 2007. TLR signaling mediated by MyD88 is required for a protective innate immune response by neutrophils to Citrobacter rodentium. J Immunol 179(1):566-77. [PubMed: 17579078]  [MGI Ref ID J:149408]

Liu B; Yang Y; Dai J; Medzhitov R; Freudenberg MA; Zhang PL; Li Z. 2006. TLR4 up-regulation at protein or gene level is pathogenic for lupus-like autoimmune disease. J Immunol 177(10):6880-8. [PubMed: 17082602]  [MGI Ref ID J:140487]

Martinon F; Chen X; Lee AH; Glimcher LH. 2010. TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat Immunol 11(5):411-8. [PubMed: 20351694]  [MGI Ref ID J:158967]

Sakata Y; Dong JW; Vallejo JG; Huang CH; Baker JS; Tracey KJ; Tacheuchi O; Akira S; Mann DL. 2007. Toll-like receptor 2 modulates left ventricular function following ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 292(1):H503-9. [PubMed: 16980352]  [MGI Ref ID J:119941]

Shi S; Blumenthal A; Hickey CM; Gandotra S; Levy D; Ehrt S. 2005. Expression of many immunologically important genes in Mycobacterium tuberculosis-infected macrophages is independent of both TLR2 and TLR4 but dependent on IFN-alphabeta receptor and STAT1. J Immunol 175(5):3318-28. [PubMed: 16116224]  [MGI Ref ID J:113220]

Smoak KA; Aloor JJ; Madenspacher J; Merrick BA; Collins JB; Zhu X; Cavigiolio G; Oda MN; Parks JS; Fessler MB. 2010. Myeloid differentiation primary response protein 88 couples reverse cholesterol transport to inflammation. Cell Metab 11(6):493-502. [PubMed: 20519121]  [MGI Ref ID J:160911]

Tesar BM; Jiang D; Liang J; Palmer SM; Noble PW; Goldstein DR. 2006. The role of hyaluronan degradation products as innate alloimmune agonists. Am J Transplant 6(11):2622-35. [PubMed: 17049055]  [MGI Ref ID J:135969]

Togbe D; Aurore G; Noulin N; Quesniaux VF; Schnyder-Candrian S; Schnyder B; Vasseur V; Akira S; Hoebe K; Beutler B; Ryffel B; Couillin I. 2006. Nonredundant roles of TIRAP and MyD88 in airway response to endotoxin, independent of TRIF, IL-1 and IL-18 pathways. Lab Invest 86(11):1126-35. [PubMed: 16983331]  [MGI Ref ID J:114842]

Wei B; Su TT; Dalwadi H; Stephan RP; Fujiwara D; Huang TT; Brewer S; Chen L; Arditi M; Borneman J; Rawlings DJ; Braun J. 2008. Resident enteric microbiota and CD8(+) T cells shape the abundance of marginal zone B cells. Eur J Immunol 38(12):3411-3425. [PubMed: 19009526]  [MGI Ref ID J:141389]

Zhou R; Zhang R; Sun Y; Platt S; Szczotka-Flynn L; Pearlman E. 2012. Innate immune regulation of Serratia marcescens-induced corneal inflammation and infection. Invest Ophthalmol Vis Sci 53(11):7382-8. [PubMed: 23033384]  [MGI Ref ID J:214276]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryHeterozygotes or homozygotes may be bred.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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