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However, the roles of TAS2Rs in these responses remain to be tested and established genetically. Here, we employed the CRISPR\/Cas9 gene\u2010editing technique to delete three bitter taste receptors\u2014<jats:italic>Tas2r143<\/jats:italic>\/<jats:italic>Tas2r135<\/jats:italic>\/<jats:italic>Tas2r126<\/jats:italic> (i.e., <jats:italic>Tas2r<\/jats:italic> triple knockout [TKO]) in mice. The fidelity and effectiveness of the <jats:italic>Tas2r<\/jats:italic> deletions were validated genetically at DNA and messenger RNA levels and functionally based on the tasting of TAS2R135 and TAS2R126 agonists. Bitter tastants are known to relax airways completely. However, TAS2R135 or TAS2R126 agonists either failed to induce relaxation of pre\u2010contracted airways in wild\u2010type mice and <jats:italic>Tas2r<\/jats:italic> TKO mice or relaxed them dose\u2010dependently, but to the same extent in both types of mice. These results indicate that TAS2Rs are not required for bitter tastant\u2010induced bronchodilation. The <jats:italic>Tas2r<\/jats:italic> TKO mice also provide a valuable model to resolve whether TAS2Rs mediate bitter tastant\u2010induced responses in many other extraoral tissues.<\/jats:p>","DOI":"10.1002\/jcp.30315","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T17:21:16Z","timestamp":1612977676000},"page":"6407-6423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Genetic deletion of the <i>Tas2r143<\/i>\/<i>Tas2r135<\/i>\/<i>Tas2r126<\/i> cluster reveals that TAS2Rs may not mediate bitter tastant\u2010induced bronchodilation"],"prefix":"10.1002","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8953-1494","authenticated-orcid":false,"given":"Ping","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Physiological Systems University of Massachusetts Medical School  Worcester Massachusetts 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