Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac

The ability to taste the sweetness of carbohydrate-rich foodstuffs has a cr itical role in the nutritional status of humans. Although several component s of bitter transduction pathways have been identified(1-6), the receptors and other sweet transduction elements remain unknown. The Sac locus in mous e, mapped to the distal end of chromosome 4 (refs. 7-9), is the major deter minant of differences between sweet-sensitive and -insensitive strains of m ice in their responsiveness to saccharin, sucrose and other sweeteners(10-1 3). To identify the human Sac locus, we searched for candidate genes within a region of approximately one million base pairs of the sequenced human ge nome syntenous to the region of Sac in mouse. From this search, we identifi ed a likely candidate: T1R3, a previously unknown G protein-coupled recepto r (GPCR) and the only GPCR in this region. Mouse Tas1r3 (encoding T1r3) map s to within 20,000 bp of the marker closest to Sac (ref. 9) and, like human TA5IR3, is expressed selectively in taste receptor cells. By comparing the sequence of Tas1r3 from several independently derived strains of mice, we identified a specific polymorphism that assorts between taster and non-tast er strains. According to models of its structure. T1r3 from non-tasters is predicted to have an extra amino-terminal glycosylation site that, if used, would interfere with dimerization.