Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   12-DEC-08 Species laboratory mouse Generation N9+N1F9 (09-MAR-12) Generation Definitions   Donating Investigator Andrew D Luster,   Massachusetts General Hospital-East

Description
Mice homozygous for this BLTR (BLT1)-deficient allele are viable and fertile. Northern blot analysis of neutrophils, macrophages, lymph nodes, lungs, and spleens isolated from homozygous mice show absence of the normal transcript and presence of the expected larger transcript (due to the insertion of the neomycin resistance cassette in exon 2 of the targeted gene), albeit at lower levels than the wild type transcript. Homozygous disruption of this allele confers impaired leukocyte function (chemotaxis, recruitment, firm adhesion). For example, homozygotes exhibit substantially diminished recruitment of eosinophils in a model of peritonitis, effector T cells in a model of allergic pulmonary inflammation, and neutrophils in a model of rheumatoid arthritis. As the G protein-coupled receptor BLTR/BLT1 is expressed on myeloid leukocytes (including neutrophils, macrophages, eosinophils, T cell lymphomas, and effector T cells (TH1 CD4⁺ cells, TH2 CD4⁺ cells, and effector memory CD8⁺ cells) during CD4⁺ migration/recruitment from the lymphoid compartment into peripheral tissues), these BLTR/BLT1 mutant mice may be useful for studying leukocyte function in inflammation, as well as the role of the LTB4-BLT1 pathway linking early immune system activation and multiple classes of acquired immune effector cells.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector was designed to insert a neomycin resistance cassette into exon 2 (near the proposed initiating methionine) of the targeted gene. This construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric animals were crossed to C57BL/6 mice. Heterozygotes were then backcrossed to C57BL/6NCrl for at least nine generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	005304 C57BL/6NJ	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Ltb4r1^tm1Adl/Ltb4r1^tm1Adl

        involves: 129S4/SvJae * C57BL/6

• immune system phenotype
• abnormal leukocyte migration
  • after 96 hours, leukocyte recruitment in thioglycollate-induced peritonitis is 61% of wild-type   (MGI Ref ID J:63873)
• • abnormal leukocyte adhesion
    • LTB4 fails to decrease rolling of leukocytes as in wild-type mice   (MGI Ref ID J:63873)
• abnormal macrophage physiology
  • thioglycollate-elicited peritoneal neutrophils and macrophages fail to exhibit calcium fluxes unlike in wild-type controls   (MGI Ref ID J:63873)
  • however, calcium fluxes in response to chemokines is normal   (MGI Ref ID J:63873)
• abnormal neutrophil physiology
  • thioglycollate-elicited peritoneal neutrophils and macrophages fail to exhibit calcium fluxes unlike in wild-type controls   (MGI Ref ID J:63873)
  • however, calcium fluxes in response to chemokines is normal   (MGI Ref ID J:63873)
• • impaired neutrophil chemotaxis
    • neutrophils fail to exhibit chemotaxis in response to LTB4 unlike wild-type cells   (MGI Ref ID J:63873)
• impaired eosinophil recruitment
  • after 48 hours, eosinophil recruitment in thioglycollate-induced peritonitis is 33% of wild-type   (MGI Ref ID J:63873)
• cellular phenotype
• abnormal leukocyte migration
  • after 96 hours, leukocyte recruitment in thioglycollate-induced peritonitis is 61% of wild-type   (MGI Ref ID J:63873)
• • abnormal leukocyte adhesion
    • LTB4 fails to decrease rolling of leukocytes as in wild-type mice   (MGI Ref ID J:63873)
• impaired neutrophil chemotaxis
  • neutrophils fail to exhibit chemotaxis in response to LTB4 unlike wild-type cells   (MGI Ref ID J:63873)

View Research Applications

Research Applications

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

Cancer Research
Defects in Cell Adhesion Molecules

Cell Biology Research
Defects in Cell Adhesion Molecules

Developmental Biology Research
Defects in Cell Adhesion Molecules
Internal/Organ Defects
      Lymphoid Tissue Defects
      hematopoietic defects
Lymphoid Tissue Defects
      hematopoietic defects

Hematological Research
Hematopoietic Defects
Immunological Defects
Neutrophil Defects

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      Neutrophil Defects
      T cell deficiency
      specific T cell deficiency
Inflammation
      Neutrophil defects
Lymphoid Tissue Defects
      Lymphocyte Homing
      hematopoietic development

Internal/Organ Research
Lymphoid Tissue Defects
      T cell deficiency

Research Tools
Cancer Research
      T cell deficiency
      production of T cells and hybridoma
      specific T cell deficiency
Cell Biology Research
Hematological Research
Immunology and Inflammation Research
      T cell deficiency
      production of T cell lines and hybridomas
      specific T cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ltb4r1tm1Adl
Allele Name		targeted mutation 1, Andrew D Luster
Allele Type		Targeted (knock-out)
Common Name(s)		BLT1-; BLTR-;
Mutation Made By		Andrew Luster,   Massachusetts General Hospital-East
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Ltb4r1, leukotriene B4 receptor 1
Chromosome		14
Gene Common Name(s)		BLT1; BLTR; CMKRL1; GPR16; LTBR1; P2RY7; P2Y7; mBLTR;
Molecular Note		The gene was disrupted by insertion of a neomycin resistance cassette into exon 2 just 3' of the translation initiation codon via homologous recombination. Northern blot analysis detected a mutant transcript containing the neomycin insert in neutrophils,macrophages, lymph nodes, lung, and spleen from homozygous mutant animals. [MGI Ref ID J:63873]

Genotyping

Genotyping Information

Genotyping Protocols

Ltb4r1^tm1Adl, Melt Curve Analysis
Ltb4r1^tm1Adl, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Tager AM; Dufour JH; Goodarzi K; Bercury SD; von Andrian UH; Luster AD. 2000. BLTR mediates leukotriene B(4)-induced chemotaxis and adhesion and plays a dominant role in eosinophil accumulation in a murine model of peritonitis [see comments] J Exp Med 192(3):439-46. [PubMed: 10934232]  [MGI Ref ID J:63873]

Additional References

Reese TA; Liang HE; Tager AM; Luster AD; Van Rooijen N; Voehringer D; Locksley RM. 2007. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature 447(7140):92-6. [PubMed: 17450126]  [MGI Ref ID J:122735]

Tager AM; Bromley SK; Medoff BD; Islam SA; Bercury SD; Friedrich EB; Carafone AD; Gerszten RE; Luster AD. 2003. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nat Immunol 4(10):982-90. [PubMed: 12949531]  [MGI Ref ID J:85816]

Ltb4r1^tm1Adl related

Ahluwalia N; Lin AY; Tager AM; Pruitt IE; Anderson TJ; Kristo F; Shen D; Cruz AR; Aikawa M; Luster AD; Gerszten RE. 2007. Inhibited aortic aneurysm formation in BLT1-deficient mice. J Immunol 179(1):691-7. [PubMed: 17579092]  [MGI Ref ID J:143153]

Binstadt BA; Patel PR; Alencar H; Nigrovic PA; Lee DM; Mahmood U; Weissleder R; Mathis D; Benoist C. 2006. Particularities of the vasculature can promote the organ specificity of autoimmune attack. Nat Immunol 7(3):284-92. [PubMed: 16444258]  [MGI Ref ID J:112604]

Chen M; Lam BK; Luster AD; Zarini S; Murphy RC; Bair AM; Soberman RJ; Lee DM. 2010. Joint tissues amplify inflammation and alter their invasive behavior via leukotriene B4 in experimental inflammatory arthritis. J Immunol 185(9):5503-11. [PubMed: 20876351]  [MGI Ref ID J:165193]

Chou RC; Kim ND; Sadik CD; Seung E; Lan Y; Byrne MH; Haribabu B; Iwakura Y; Luster AD. 2010. Lipid-cytokine-chemokine cascade drives neutrophil recruitment in a murine model of inflammatory arthritis. Immunity 33(2):266-78. [PubMed: 20727790]  [MGI Ref ID J:163913]

Eisenring M; vom Berg J; Kristiansen G; Saller E; Becher B. 2010. IL-12 initiates tumor rejection via lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46. Nat Immunol 11(11):1030-8. [PubMed: 20935648]  [MGI Ref ID J:166535]

Goodarzi K; Goodarzi M; Tager AM; Luster AD; von Andrian UH. 2003. Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues. Nat Immunol 4(10):965-73. [PubMed: 12949533]  [MGI Ref ID J:85831]

Heller EA; Liu E; Tager AM; Sinha S; Roberts JD; Koehn SL; Libby P; Aikawa ER; Chen JQ; Huang P; Freeman MW; Moore KJ; Luster AD; Gerszten RE. 2005. Inhibition of atherogenesis in BLT1-deficient mice reveals a role for LTB4 and BLT1 in smooth muscle cell recruitment. Circulation 112(4):578-86. [PubMed: 16043658]  [MGI Ref ID J:117166]

Kim ND; Chou RC; Seung E; Tager AM; Luster AD. 2006. A unique requirement for the leukotriene B4 receptor BLT1 for neutrophil recruitment in inflammatory arthritis. J Exp Med 203(4):829-35. [PubMed: 16567386]  [MGI Ref ID J:123752]

Medoff BD; Seung E; Wain JC; Means TK; Campanella GS; Islam SA; Thomas SY; Ginns LC; Grabie N; Lichtman AH; Tager AM; Luster AD. 2005. BLT1-mediated T cell trafficking is critical for rejection and obliterative bronchiolitis after lung transplantation. J Exp Med 202(1):97-110. [PubMed: 15998790]  [MGI Ref ID J:100652]

Medoff BD; Tager AM; Jackobek R; Means TK; Wang L; Luster AD. 2006. Antibody-antigen interaction in the airway drives early granulocyte recruitment through BLT1. Am J Physiol Lung Cell Mol Physiol 290(1):L170-8. [PubMed: 16126787]  [MGI Ref ID J:104882]

Miyahara N; Takeda K; Miyahara S; Taube C; Joetham A; Koya T; Matsubara S; Dakhama A; Tager AM; Luster AD; Gelfand EW. 2005. Leukotriene B4 receptor-1 is essential for allergen-mediated recruitment of CD8+ T cells and airway hyperresponsiveness. J Immunol 174(8):4979-84. [PubMed: 15814727]  [MGI Ref ID J:98154]

Oyoshi MK; He R; Li Y; Mondal S; Yoon J; Afshar R; Chen M; Lee DM; Luo HR; Luster AD; Cho JS; Miller LS; Larson A; Murphy GF; Geha RS. 2012. Leukotriene b4-driven neutrophil recruitment to the skin is essential for allergic skin inflammation. Immunity 37(4):747-58. [PubMed: 23063331]  [MGI Ref ID J:188555]

Reese TA; Liang HE; Tager AM; Luster AD; Van Rooijen N; Voehringer D; Locksley RM. 2007. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature 447(7140):92-6. [PubMed: 17450126]  [MGI Ref ID J:122735]

Serezani CH; Aronoff DM; Sitrin RG; Peters-Golden M. 2009. FcgammaRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions. Blood 114(15):3316-24. [PubMed: 19657115]  [MGI Ref ID J:153845]

Serezani CH; Kane S; Collins L; Morato-Marques M; Osterholzer JJ; Peters-Golden M. 2012. Macrophage dectin-1 expression is controlled by leukotriene B4 via a GM-CSF/PU.1 axis. J Immunol 189(2):906-15. [PubMed: 22696442]  [MGI Ref ID J:189546]

Serezani CH; Lewis C; Jancar S; Peters-Golden M. 2011. Leukotriene B4 amplifies NF-kappaB activation in mouse macrophages by reducing SOCS1 inhibition of MyD88 expression. J Clin Invest 121(2):671-82. [PubMed: 21206089]  [MGI Ref ID J:171834]

Subbarao K; Jala VR; Mathis S; Suttles J; Zacharias W; Ahamed J; Ali H; Tseng MT; Haribabu B. 2004. Role of leukotriene B4 receptors in the development of atherosclerosis: potential mechanisms. Arterioscler Thromb Vasc Biol 24(2):369-75. [PubMed: 14656734]  [MGI Ref ID J:102012]

Tager AM; Bromley SK; Medoff BD; Islam SA; Bercury SD; Friedrich EB; Carafone AD; Gerszten RE; Luster AD. 2003. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nat Immunol 4(10):982-90. [PubMed: 12949531]  [MGI Ref ID J:85816]

Taube C; Miyahara N; Ott V; Swanson B; Takeda K; Loader J; Shultz LD; Tager AM; Luster AD; Dakhama A; Gelfand EW. 2006. The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness. J Immunol 176(5):3157-64. [PubMed: 16493075]  [MGI Ref ID J:129412]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred.
Mating System	Homozygote x Homozygote         (Female x Male)   12-DEC-08

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	005304 C57BL/6NJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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