Genetic analyses and positional cloning of the Sac locus were instrumental in discovery of the T1R sweet taste receptor genes. Studies using crosses between different inbred mouse strains have mapped the Sac locus to the subtelomeric region of mouse chromosome 4[110,123,125,126] and have shown that it affects sweetener preferences[102,106,110,122,123,125,126] and the afferent responses of gustatory nerves to sweeteners.[126,127] Our positional cloning study has shown that the Sac locus corresponds to the Tas1r3 gene[60,113,128] and that Tas1r3 sequence variants are associated with sweetener preference phenotypes in genealogically diverse mouse strains.[60,113] Additional evidence for identity of Sac and Tas1r3 was obtained in studies using congenic,[60] transgenic[38] and knockout mice.[42,43] Furthermore, allelic variants that confer different sweet taste responsiveness in mice also influenced receptor properties in in vitro assays.[41,129] We analysed association of the Tas1r3 sequence variants with saccharin preferences in a large panel of genealogically diverse inbred mouse strains.[113] This analysis has identified an amino acid substitution of isoleucine to threonine at position 60 (I60T) as a candidate causative variant for phenotypical variation in sweet taste preferences. Because this sequence variant is
