Polymorphisms in the Taste Receptor Gene (Tas1r3) Region Are Associated with Saccharin Preference in 30 Mouse Strains

Abstract

The results of recent studies suggest that the mouse Sac (saccharin preference) locus is identical to the Tas1r3 (taste receptor) gene. The goal of this study was to identify Tas1r3 sequence variants associated with saccharin preference in a large number of inbred mouse strains. Initially, we sequenced ϳ6.7 kb of the Tas1r3 gene and its flanking regions from six inbred mouse strains with high and low saccharin preference, including the strains in which the Sac alleles were described originally (C57BL/6J, Sac b ; DBA/2J, Sac d ). Of the 89 sequence variants detected among these six strains, eight polymorphic sites were significantly associated with preferences for 1.6 mM saccharin. Next, each of these eight variant sites were genotyped in 24 additional mouse strains. Analysis of the genotype-phenotype associations in all 30 strains showed the strongest association with saccharin preference at three sites: nucleotide (nt) Ϫ791 (3 bp insertion/deletion), nt ϩ135 (Ser45Ser), and nt ϩ179 (Ile60Thr). We measured Tas1r3 gene expression, transcript size, and T1R3 immunoreactivity in the taste tissue of two inbred mouse strains with different Tas1r3 haplotypes and saccharin preferences. The results of these experiments suggest that the polymorphisms associated with saccharin preference do not act by blocking gene expression, changing alternative splicing, or interfering with protein translation in taste tissue. The amino acid substitution (Ile60Thr) may influence the ability of the protein to form dimers or bind sweeteners. Here, we present data for future studies directed to experimentally confirm the function of these polymorphisms and highlight some of the difficulties of identifying specific DNA sequence variants that underlie quantitative trait loci.

Voluntary ethanol consumption in 22 inbred mouse strains

“…However, recent findings indicate that mice with a null mutation in one of three genes that are important for taste transduction (Gnat3, Tas1r3, or Trpm5) exhibited reduced consumption of and preference for alcohol (6 -12%) and saccharin (0.033 -0.066%) solutions (Blednov et al, 2007). Since polymorphisms in the Tas1r3 gene (believed to be identical to the mouse Sac locus, important for saccharin preference) were strongly associated with saccharin preference in a panel of 30 inbred strains (Reed et al, 2004), it is possible that polymorphisms in genes important for taste transduction contribute to the low alcohol consumption in select inbred strains. It should be noted that some strains may respond to adulteration of ethanol solutions with other compounds by increasing intake, as D2 mice have been shown to increase their intake of and two-bottle preference for ethanol when it was added to non-alcoholic beer (Grisel et al, 2007).…”

Genetics of Taste and Smell

“…88 Alleles in the promoter region of this same gene predict how well people can sort a range of sucrose concentrations into the correct order, 89 but it is not known whether these sensitivity alleles are related to preference. Other genes and their alleles probably also contribute to genetic differences in sweet perception (e.g., second messenger molecules like gustducin).…”

Diverse tastes: Genetics of sweet and bitter perception

“…The taste receptor protein T1R3 was discovered with the aid of mapping experiments in mice, which exploited the differences in sweetness preference of inbred strains [28]. These differences among inbred mice were due to a naturally occurring allele of Tas1r3 [26,[29][30][31][32][33][34].…”

“…Alleles of Tas1r3 correlate with sweetener intake, e.g., [34]. Recordings of the peripheral taste nerves suggest that mice with the low-preference Tas1r3 alleles exhibit lower nerve firing in response to saccharin or other sweeteners [35,36].…”

“…Also, when both genes, Tas1r2 and Tas1r3, are knocked out, the response to sweeteners disappears [38]. Although there are a number of Tas1r3 alleles that correlate with sweet intake [34], studies of specific DNA variants in cellbased assay systems have identified that exchange of isoleucine to threonine at position 60 of T1R3 as the likely reason for the low saccharin preference in mice [39]. Taken together, these lines of evidence suggest that differences in the DNA sequence of taste receptors can lead to altered taste perception, at least in mice.…”