B6.129S4-Del(14Ltb4r2-Ltb4r1)1Bodd/J

Stock number: 031621
Product name: BLT1/BLT2^-
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research

Description

BLT1/BLT2^-/- mice have an EGFP sequence and a neo cassette replacing 6 Kb of coding region, including most of the Ltb4r1 and Ltb4r2 genes, and the untranscribed region between both open reading frames. This strain is useful for studying rheumatoid arthritis (RA).

Detailed description

BLT1/BLT2^-/- mice have an EGFP sequence and a neo cassette replacing 6 Kb of coding region, including most of the Ltb4r1 and Ltb4r2 genes, and the untranscribed region between both open reading frames. BLT1 and BLT2 encode G protein-coupled receptors for Leukotriene B4. Leukotrienes are lipid mediators synthesized from arachidonic acid by lipoxygenase enzymes. They are important in inflammatory signaling pathways. Specifically, Leukotriene B4 acts as a chemoattractant of leukocytes. It promotes inflammation by stimulating CD11b up-regulation and adhesion of leukocytes, emigration of leukocytes from the bloodstream, neutrophil activation leading to respiratory burst, degranulation, and release of enzymes. BLT1 is expressed in a variety of leukocytes including neutrophils, monocyte/macrophages, eosinophils, mast cells, and activated T lymphocytes. BLT2 is a low-affinity receptor more widely expressed but still present in neutrophils, monocytes, and mast cells. In studies of rheumatoid arthritis (RA) high levels of BLT2 mRNA expression are observed in actively inflamed synovial tissue from patients with RA, whereas leukocytes infiltrating synovial fluid predominantly express BLT1 mRNA.

Mice that are homozygous for this allele are viable and fertile. These mice are resistant to collagen induced arthritis (CIA). The number and development of leukocyte subpopulations is normal. The EGFP in this strain is non-functional and it is unknown if it is detectable by immunohistochemistry. Weak EGFP expression is evident in platelets by flow cytometry.

Development

The BLT1/BLT2^- targeting vector was designed to replace 6 Kb of coding region, including most of the leukotriene B4 receptor 1 (Ltb4r1) and leukotriene B4 receptor 2 (Ltb4r2) genes, and the untranscribed region between both open reading frames, with an enhanced green fluorescent protein sequence (EGFP) and a neomycin resistance (neo) cassette. The construct was electroporated into 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric mice were bred with C57BL/6J mice for at least 9 generations. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Del(14Ltb4r2-Ltb4r1)1Bodd
Name: deletion, Chr 14, Bodduluri Haribabu 1
MGI accession ID: MGI:3775059
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: BLT1/BLT2^-; Del1Bodd; Ltb4r1/Ltb4r2^tm2Bodd
Marker symbol: Del(14Ltb4r2-Ltb4r1)1Bodd
Marker name: deletion, Chr 14, Bodduluri Haribabu 1
Chromosome: 14
Strain of origin: 129S4/SvJaeSor
Molecular note: 6 Kb of the coding region and the untranscribed region between both open reading frames were replaced with an EGFP-neo cassette. The absence of transcript from either open reading frame was confirmed by northern blot analysis on spleen, liver, neutrophil and macrophage extracts.