B6.129S4-Ltb4r1^tm1Adl/J

Stock number: 008102
Product name: BLTR KO
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

Homozygous mice for this leukotriene B4 receptor (Ltb4r1, commonly referred to as BLTR) knock-out exhibit substantially diminished recruitment of eosinophils, effector T cells, and neutrophil; and 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.

 

Detailed 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.

Allele

Symbol: Ltb4r1^tm1Adl
Name: targeted mutation 1, Andrew D Luster
MGI accession ID: MGI:2385786
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ltb4r1
Marker name: leukotriene B4 receptor 1
Chromosome: 14
Strain of origin: 129S4/SvJae
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.