The mechanisms underlying sweet taste in mammals have been elusive. Althoug
h numerous studies have implicated G proteins in sweet taste detection, the
expected G protein-coupled receptors have not been found. Here we describe
a candidate taste receptor gene, T1r3, that is located at or near the mous
e Sac locus, a genetic locus that controls the detection of certain sweet t
astants. T1R3 differs in amino acid sequence in mouse strains with differen
t Sac phenotypes ('tasters' versus 'nontasters'). In addition, a perfect co
rrelation exists between two different T1r3 alleles and Sac phenotypes in r
ecombinant inbred mouse strains. The T1r3 gene is expressed in a subset of
taste cells in circumvallate, foliate and fungiform taste papillae. In circ
umvallate and foliate papillae, most T1r3-expressing cells also express a g
ene encoding a related receptor, T1R2 raising the possibility that these ce
lls recognize more than one ligand, or that the two receptors function as h
eterodimers.