Abstract
BackgroundThe detection of bitter-tasting compounds by the gustatory system is thought to alert animals to the presence of potentially toxic food. Some, if not all, bitter stimuli activate specific taste receptors, the T2Rs, which are expressed in subsets of taste receptor cells on the tongue and palate. However, there is evidence for both receptor-dependent and -independent transduction mechanisms for a number of bitter stimuli, including quinine hydrochloride (QHCl) and denatonium benzoate (DB).ResultsWe used brief-access behavioral taste testing of BXD/Ty recombinant inbred (RI) mouse strains to map the major quantitative trait locus (QTL) for taste sensitivity to QHCl. This QTL is restricted to a ~5 Mb interval on chromosome 6 that includes 24 genes encoding T2Rs (Tas2rs). Tas2rs at this locus display in total 307 coding region single nucleotide polymorphisms (SNPs) between the two BXD/Ty RI parental strains, C57BL/6J (quinine-sensitive) and DBA/2J (quinine insensitive); approximately 50% of these mutations are silent. Individual RI lines contain exclusively either C57BL/6J or DBA/2J Tas2r alleles at this locus, and RI lines containing C57BL/6J Tas2r alleles are more sensitive to QHCl than are lines containing DBA/2J alleles. Thus, the entire Tas2r cluster comprises a large haplotype that correlates with quinine taster status.ConclusionThese studies, the first using a taste-salient assay to map the major QTL for quinine taste, indicate that a T2R-dependent transduction cascade is responsible for the majority of strain variance in quinine taste sensitivity. Furthermore, the large number of polymorphisms within coding exons of the Tas2r cluster, coupled with evidence that inbred strains exhibit largely similar bitter taste phenotypes, suggest that T2R receptors are quite tolerant to variation.
Highlights
The detection of bitter-tasting compounds by the gustatory system is thought to alert animals to the presence of potentially toxic food
Taste testing Previous efforts to map quantitative trait locus (QTL) for bitter taste have utilized consumption tests that may be confounded by the contributions of post-ingestive effects [29]
Subsequent taste testing of BXD recombinant inbred (RI) lines was restricted to these two concentrations (1 and 3 mM for both quinine hydrochloride (QHCl) and denatonium benzoate (DB))
Summary
The detection of bitter-tasting compounds by the gustatory system is thought to alert animals to the presence of potentially toxic food. If not all, bitter stimuli activate specific taste receptors, the T2Rs, which are expressed in subsets of taste receptor cells on the tongue and palate. Two families of G protein-coupled receptors (GPCRs) expressed in subpopulations of taste receptor cells (TRCs) of the gustatory epithelium have been implicated in the detection and transduction of sweet, bitter and umami (i.e., glutamate) taste: T1Rs for (page number not for citation purposes). BMC Genetics 2005, 6:32 http://www.biomedcentral.com/1471-2156/6/32 sweet-and umami-tasting stimuli [1,2,3,4,5,6,7,8], and T2Rs for bitter-tasting compounds [9,10,11]. Thirty-three human Tas2rs (including 8 pseudogenes) and thirty-six mouse Tas2rs (including 3 pseudogenes in C57BL/6J mice) have been identified [9,11,19], and several of these respond to particular bitter stimuli in heterologous expression assays [10,20,21,22,23], or represent a strong candidate gene for a specific bitter taste quantitative trait [18,24,25]
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