Genetic deletion of the Tas2r143/Tas2r135/Tas2r126 cluster reveals that TAS2Rs may not mediate bitter tastant-induced bronchodilation.

Journal Article (Journal Article)

Bitter taste receptors (TAS2Rs) and their signaling elements are detected throughout the body, and bitter tastants induce a wide variety of biological responses in tissues and organs outside the mouth. However, the roles of TAS2Rs in these responses remain to be tested and established genetically. Here, we employed the CRISPR/Cas9 gene-editing technique to delete three bitter taste receptors-Tas2r143/Tas2r135/Tas2r126 (i.e., Tas2r triple knockout [TKO]) in mice. The fidelity and effectiveness of the Tas2r 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-contracted airways in wild-type mice and Tas2r TKO mice or relaxed them dose-dependently, but to the same extent in both types of mice. These results indicate that TAS2Rs are not required for bitter tastant-induced bronchodilation. The Tas2r TKO mice also provide a valuable model to resolve whether TAS2Rs mediate bitter tastant-induced responses in many other extraoral tissues.

Full Text

Duke Authors

Cited Authors

  • Lu, P; ElMallah, MK; Liu, Z; Wu, C; Chen, J; Lifshitz, LM; ZhuGe, R

Published Date

  • September 2021

Published In

Volume / Issue

  • 236 / 9

Start / End Page

  • 6407 - 6423

PubMed ID

  • 33559206

Pubmed Central ID

  • PMC8223514

Electronic International Standard Serial Number (EISSN)

  • 1097-4652

Digital Object Identifier (DOI)

  • 10.1002/jcp.30315


  • eng

Conference Location

  • United States