Polymorphisms of the mouse Tas1r3 gene are related to sweetener preferences in 30 strains of mice
A.A. Bachmanov1, S. Li1, X. Li1, M.G. Tordoff1, D.B. West2, J.D. Ohmen2, D.R. Reed1, G.K. Beauchamp1
1Monell Chemical Senses Center, Philadelphia, PA
2Pfizer Global Research and Development, Alameda, CA
Positional cloning has determined that a taste receptor gene, Tas1r3, is identical to the mouse saccharin preference (Sac) locus. The goal of this study was to analyze the relationship between sequence variants of Tas1r3 and sweetener preferences. We characterized saccharin preferences, and sequenced the DNA including and surrounding the Tas1r3 gene of 30 inbred mouse strains. Sixty sequence variants were detected; several of them had significant associations with saccharin preference. In most of the strains, these variants formed two haplotypes, with all alleles being common either to high-preferring or low-preferring strains. In a few strains, the haplotypes were recombinant. Analysis of these recombinant haplotypes suggests that the best match between the sequence variants and saccharin preferences occurs at nt positions 135 (silent S45S) and 179 (missense I60T), with the I60T variant being most likely to affect the function of the T1R3 receptor. A substantial portion of the strain differences in saccharin preference remained unaccounted for by allelic variation at Tas1r3, and thus must be attributed to variation at other genetic loci. This indicates that sweetener preference has a complex genetic determination and emphasizes the importance of identification of these other genes involved in sweetener preferences, which is a goal of ongoing studies in our laboratory.
Bachmanov AA, Li X, Reed DR, Ohmen JD, Li S, Chen Z, Tordoff MG, de Jong PJ, Wu C, West DB, Chatterjee A, Ross DA, Beauchamp GK (2001) Positional cloning of the mouse saccharin preference (Sac) locus. Chemical Senses 26: 925-933. Li X, Bachmanov AA, Li S, Chen Z, Tordoff MG, Beauchamp GK, de Jong PJ, Wu C, Chen, L, West DB, Chatterjee A, Ross DA, Ohmen JD, Reed DR. (2002) Genetic, physical and comparative map of the subtelomeric region of mouse chromosome 4. Mammalian Genome 13: 5-19.
[Supported by NIH grants R01DC00882 (GKB), R03DC03509, R01DC04188 and R01DK55853 (DRR), R01AA11028 (MGT) and R03DC03853 (AAB)]