Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Heterozygote         (Female x Male) Species laboratory mouse Generation N9+ (12-AUG-08)   Donating Investigator Andrew 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

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

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

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)
Internal/Organ Defects (hematopoietic defects)
Lymphoid Tissue Defects (hematopoietic defects)

Hematological Research
Hematopoietic Defects
Immunological Defects
Neutrophil Defects

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

Internal/Organ Research
Lymphoid Tissue Defects (T cell deficiency)

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

Genes & Alleles

Gene & Allele Information

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, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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

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]

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]

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]

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           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred.
Mating System	Heterozygote x Heterozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	005304 C57BL/6NJ	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

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

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.