These hCysLT1R mice express a transgene containing a 2.8Kb sequence encoding the human cysteinyl leukotriene receptor 1, and respond to leukotriene D4 challenge with elevated intracellular calcium in smooth muscle cells of the airway.
Colin D. Funk, Queen's University
These transgenic mice express the human cysteinyl leukotriene receptor 1 under the control of the mouse actin, alpha 2, smooth muscle, aorta, promoter. Transgene expression is detected in stomach, bladder, intestine, uterus, and lung, but not in heart or skeletal muscle by RT-PCR analysis. Ribonuclease protection assay analysis, specific for human cysteinyl leukotriene receptor 1, detects transgene expression in lung tissue from mutant mice. Fluorescent in situ hybridization detects transgene expression in the peribronchiolar regions and small blood vessels of the lungs. Cultured isolated smooth muscle cells from tracheal explants have 26 times greater cysteinyl leukotriene receptor 1 density than wildtype, as measured by radioligand binding assays. Transgenic mice respond to leukotriene D4 (LTD4) challenge with elevated intracellular calcium in smooth muscle cells of the airway. Allergenic sensitization and challenge induces increased response to LTD4. This mutant mouse strain may be useful in studies of allergic airway inflammation, asthma or airway hyperrsponsiveness (AHR).
A transgenic construct containing a 2.8Kb sequence encoding the human cysteinyl leukotriene receptor 1 under the control of the mouse actin, alpha 2, smooth muscle, aorta, promoter and SV40 polyadenylation site sequence was injected into fertilized B6SJLF1 mouse eggs. Founder animals were bred to B6SJLF1 mice. The mice were then backcrossed to BALB/c for 9 generations.
|Expressed Gene||CYSLTR1, cysteinyl leukotriene receptor 1, human|
|Site of Expression|
|Allele Name||transgene insertion 31, Colin D Funk|
|Allele Type||Transgenic (Inserted expressed sequence, Humanized sequence)|
|Gene Symbol and Name||Tg(Acta2/CYSLTR1)31Fun, transgene insertion 31, Colin D Funk|
|Promoter||Acta2, actin, alpha 2, smooth muscle, aorta, mouse, laboratory|
|Expressed Gene||CYSLTR1, cysteinyl leukotriene receptor 1, human|
|Strain of Origin||(C57BL/6 x SJL)F2|
|General Note||Three founder lines, designated lines 1, 4 and 31, were established. Yang and colleagues (2004) performed all analyses on lines 1 and 31, whose transgene copy number and expression levels were virtually identical; some analyses also included line 4, estimated to carry approximately 10 copies of the transgene. As both C57BL/6 and SJL mice exhibit relatively mild responses to airway challenge, Tg31Fun was crossed onto the commonly hyperresponsive BALB/c strain to examine differences in response between transgenic mice of the mixed C57BL/6-SJL versus BALB/c backgrounds.|
|Molecular Note||The transgene comprises 3.6 kb of mouse genomic DNA including the promoter, first exon, first intron and part of the second exon of the gene encoding actin, alpha 2, smooth muscle, aorta fused to a 1.1 kb human genomic DNA fragment encoding cysteinyl leukotriene receptor 1, followed by the SV40 polyadenylation signal. Human CYSTR1 RNA was detected in stomach, bladder, intestine, uterus and lung, but not in cardiac or skeletal muscle of transgenic mice; in lung, expression was shown to be restricted to airway and vascular smooth muscle. Binding of labeled leukotriene D4 revealed receptor density in smooth muscle cells cultured from lungs of transgenic mice to be 37-fold that in wildtype cells.|
When held in a live colony, this strain may be maintained as a hemizygote.
When using the hCysLT1R mouse strain in a publication, please cite the originating article(s) and include JAX stock #005129 in your Materials and Methods section.
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