Homozygous CysLT2 receptor knock-out mice on the C57BL/6 background develop an attenuated response to induced IgE-dependent passive cutaneous anaphylaxis (PCA) and bleomycin-induced pulmonary fibrosis.
Yoshihide Kanaoka, Brigham and Women's Hospital
Cysltr2 (cysteinyl leukotriene receptor 2) encodes a member of the superfamily of G protein-coupled receptors and functions as a receptor for the cysteinyl leukotrienes. Cysteinyl leukotrienes are lipid mediators associated with allergic and asthmatic inflammatory responses. The CysLT2 receptor knock-out mice contain a neomycin cassette inserted into exon 6 of Cysltr2. Homozygous null mice are viable and fertile. IgE-dependent passive cutaneous anaphylaxis (PCA) induced in the ear of homozygous mice on the C57BL/6 (B6) background results in a 65% reduction in vascular permeability as compared to treated controls. Similarly, intratracheal administration of bleomycin in B6 homozygous mice results in attenuated pulmonary fibrosis. Compared to treated controls bleomycin-treated mutant mice exhibit reduced septal thickening, reduced accumulation of monocyte/macrophages, giant cells, fibroblasts and eosinophils, and less extracellular matrix deposition. However, absence of the CysLT2 receptor does not affect peritoneal inflammation in mice treated with Zymosan A. In an experiment to determine the role of cysteinyl leukotrienes in Th2 immunity, sensitization and challenge of B6 Cysltr2 null mice with the house dust mite (D. farinae) results in increased eosinophilic pulmonary inflammation, serum IgE, and Th2 cytokines. The donating investigator indicates that a similar (unpublished) phenotype is observed on the BALB/c background. This strain may be useful for studying inflammatory responses.
The Cysltr2tm1Ykn allele is also available on the BALB/cJ background (Stock No. 031718).
The targeting vector was designed to use a neomycin resistance gene to disrupt exon 6 of the Cysltr2 gene. The insertion targets 264 amino acids in the N-terminal and interrupts 85% of the coding region. The construct was electroporated into C57BL/6J-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6NCrl females and maintained on a C57BL/6NCrl background. Northern blot analysis of lung, spleen and small intestine does not detect RNA transcript. Upon arrival, mice were bred to C57BL/6NJ for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Yoshihide Kanaoka|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Yoshihide Kanaoka; Cysltr2tm1Ykn|
|Gene Symbol and Name||Cysltr2, cysteinyl leukotriene receptor 2|
|Gene Synonym(s)||CYSLT2; CYSLT2R; HG57; RIKEN cDNA 2300001H05 gene; HPN321; KPG_011; 2300001H05Rik; 2300001H05Rik; PSEC0146; RSBPT32; GPCR21; hGPCR21; CysLT2; Cyslt2|
|Strain of Origin||C57BL/6|
|Molecular Note||The insertion of a neo into exon 6 interrupted 85% of the coding sequence. Northern blot showed a lack of transcript in mutant lung, spleen and small intestine.|
When maintaining a live colony, these mice are bred by homozygote sibling matings.
When using the CysLT2 receptor null mouse strain in a publication, please cite the originating article(s) and include JAX stock #031624 in your Materials and Methods section.
|Heterozygous for Cysltr2<tm1Ykn>|
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