Conclusion In conclusion, we have found that sensitivity to the bitter-tasting substance quinine, as assayed by a taste specific brief-access test, is a polygenic trait in mice. However, the major mechanism for quinine taste transduction is likely dependent on one or more T2R receptors. Most Tas2r genes in the distal chromosome 6 cluster are polymorphic across inbred strains of mice, and this cluster forms a single haplotype that correlates with quinine taste sensitivity. The numerous differences in T2R protein sequence between these two mouse strains suggests that T2Rs are broadly tuned receptors quite tolerant to sequence variation. This tolerance may help to preserve the ability of T2R-expressing, bitter-sensitive taste cells to respond to a wide array of potentially toxic stimuli.