Abstract

The mouse bitter taste receptors Tas2r143, Tas2r135, and Tas2r126 are encoded by genes that cluster on chromosome 6 and have been suggested to be expressed under common regulatory elements. Previous studies indicated that the Tas2r143/Tas2r135/Tas2r126 cluster is expressed in the heart, but other organs had not been systematically analyzed. In order to investigate the expression of this bitter taste receptor gene cluster in non-gustatory tissues, we generated a BAC (bacterial artificial chromosome) based transgenic mouse line, expressing CreERT2 under the control of the Tas2r143 promoter. After crossing this line with a mouse line expressing EGFP after Cre-mediated recombination, we were able to validate the Tas2r143-CreERT2 transgenic mouse line and monitor the expression of Tas2r143. EGFP-positive cells, indicating expression of members of the cluster, were found in about 47% of taste buds, and could also be found in several other organs. A population of EGFP-positive cells was identified in thymic epithelial cells, in the lamina propria of the intestine and in vascular smooth muscle cells of cardiac blood vessels. EGFP-positive cells were also identified in the epithelium of organs readily exposed to pathogens including lower airways, the gastrointestinal tract, urethra, vagina, and cervix. With respect to the function of cells expressing this bitter taste receptor cluster, RNA-seq analysis in EGFP-positive cells isolated from the epithelium of trachea and stomach showed expression of genes related to innate immunity. These data further support the concept that bitter taste receptors serve functions outside the gustatory system.

Highlights

  • Mammals sense a wide variety of compounds as bitter to prevent the ingestion of toxic substances

  • The murine bitter taste receptor genes Tas2r143, Tas2r135, and Tas2r126 are located in close proximity to each other on chromosome 6 without any other known genes or coding sequences located within this area

  • enhanced green fluorescent protein (EGFP)-positive cells were detected in 47 ± 7% (n = 4, mean ± SD) of all taste buds in the tongue, and these cells were positive for the taste receptor cell marker PLCß2 (Roper, 2013; Figure 2C)

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Summary

Introduction

Mammals sense a wide variety of compounds as bitter to prevent the ingestion of toxic substances. Bitter taste receptors are type 2 taste receptors (T2Rs) and belong to the superfamily of G-protein-coupled receptors (GPCRs). T2Rs are expressed primarily by type II taste receptor cells in taste buds of the tongue and share with sweet/umami taste receptors key molecules in their downstream signaling cascade. The canonical signal transduction involves activation of the Gprotein gustducin, phospholipase C (PLC) ß2 and production of inositol triphosphate (IP3). Unlike sweet/umami taste receptors, bitter taste receptors are capable of detecting diverse chemical compounds, and individual bitter taste receptors show different degrees of ligand selectivity (Lossow et al, 2016)

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