Journal
JOURNAL OF NEUROSCIENCE
Volume 24, Issue 4, Pages 938-946Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1374-03.2004
Keywords
sweet; preference; phenotype; genotype; haplotype; QTL
Categories
Funding
- NIAAA NIH HHS [R01AA11028, R01 AA011028] Funding Source: Medline
- NIDCD NIH HHS [R03DC03854, R03 DC005154, R01 DC000882, R01DC00882, R01DC04188, R03DC05154, R03DC03509] Funding Source: Medline
- NIDDK NIH HHS [R01DK55853] Funding Source: Medline
Ask authors/readers for more resources
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 similar to6.7 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) -791 (3 bp insertion/deletion), nt +135 (Ser45Ser), and nt +179 (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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available