BLT2-/- mice have an EGFP sequence and a neo cassette inserted into the coding region of the Ltb4r2 gene. This strain is useful for studying inflammation associated with arthritis.
Haribabu Bodduluri, University of Louisville
BLT2-/- mice have an EGFP sequence and a neo cassette inserted into the coding region of the leukotriene B4 receptor 2 (Ltb4r2) gene. BLT2 encodes a G protein-coupled receptor 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. BLT2 is a low-affinity receptor expressed 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.
Mice that are homozygous for this allele are viable and fertile. Although the promoter for leukotriene B4 receptor 1 (Ltb4r1) lies within the coding region of Ltb4r2, this mutation does not affect the expression of BLT1. In an autoantibody-induced inflammatory arthritis model, these mice show reduced incidence and severity of disease, including protection from bone and cartilage loss. Bone marrow-reconstitution experiments identified that loss of BLT2 expression on a bone marrow-derived cell lineage offers protection against severe disease. They are resistant to arthritis, colitis, and corneal would healing and are more susceptible to pneumolysin lung damage. The EGFP in this strain is non-functional and it is unknown if it is detectable by immunohistochemistry.
The BLT2- targeting vector was designed to insert an enhanced green fluorescent protein sequence (EGFP) and a neomycin resistance (neo) cassette into the coding region of the leukotriene B4 receptor 2 (Ltb4r2) gene. Although the promoter for leukotriene B4 receptor 1 (Ltb4r1) lies within the coding region of Ltb4r2, this mutation does not affect the expression of BLT1. 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 7 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 Name||targeted mutation 1, Bodduluri Haribabu|
|Allele Type||Targeted (Reporter, Null/Knockout)|
|Gene Symbol and Name||Ltb4r2, leukotriene B4 receptor 2|
|Strain of Origin||129S4/SvJaeSor|
|Molecular Note||A construct containing a fragment of the coding region, EGFP, and neo was inserted into the coding exon. The absence of transcript expression was confirmed by RT-PCR on bone marrow extracts.|
When maintaining a live colony, homozygous mice may be bred together.
When using the BLT2- mouse strain in a publication, please cite the originating article(s) and include JAX stock #031622 in your Materials and Methods section.