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 in the extracellular N-terminus of the predicted T1R3 protein, we proposed that it affects ligand binding.[113] This prediction was subsequently confirmed in an in vitro study showing that a corresponding site-directed mutation changes binding affinity of the T1R3 protein to several sweeteners.[129]