Single-Locus Control of Saccharin Preference in Mice

Fuller, John L.

doi:10.1093/oxfordjournals.jhered.a108452

Cited by 158 publications

(88 citation statements)

References 7 publications

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“…The Sac locus is the major genetic determinant of sweet taste preference and responsiveness to saccharin, sucrose, and other sweeteners in mice (8)(9)(10). Sac has been shown by multiple groups (2-7) to be synonymous with Tas1r3, the third member of the type I family of taste receptor genes that encodes T1r3.…”

Section: Discussionmentioning

confidence: 99%

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Glucose transporters and ATP-gated K ⁺ (K _ATP ) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells

Yee

Sukumaran

Kotha

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

189

178

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Although the heteromeric combination of type 1 taste receptors 2 and 3 (T1r2 + T1r3) is well established as the major receptor for sugars and noncaloric sweeteners, there is also evidence of T1r-independent sweet taste in mice, particularly so for sugars. Before the molecular cloning of the T1rs, it had been proposed that sweet taste detection depended on ( a ) activation of sugar-gated cation channels and/or ( b ) sugar binding to G protein-coupled receptors to initiate second-messenger cascades. By either mechanism, sugars would elicit depolarization of sweet-responsive taste cells, which would transmit their signal to gustatory afferents. We examined the nature of T1r-independent sweet taste; our starting point was to determine if taste cells express glucose transporters (GLUTs) and metabolic sensors that serve as sugar sensors in other tissues. Using RT-PCR, quantitative PCR, in situ hybridization, and immunohistochemistry, we determined that several GLUTs (GLUT2, GLUT4, GLUT8, and GLUT9), a sodium–glucose cotransporter (SGLT1), and two components of the ATP-gated K + (K ATP ) metabolic sensor [sulfonylurea receptor (SUR) 1 and potassium inwardly rectifying channel (Kir) 6.1] were expressed selectively in taste cells. Consistent with a role in sweet taste, GLUT4, SGLT1, and SUR1 were expressed preferentially in T1r3-positive taste cells. Electrophysiological recording determined that nearly 20% of the total outward current of mouse fungiform taste cells was composed of K ATP channels. Because the overwhelming majority of T1r3-expressing taste cells also express SUR1, and vice versa, it is likely that K ATP channels constitute a major portion of K + channels in the T1r3 subset of taste cells. Taste cell-expressed glucose sensors and K ATP may serve as mediators of the T1r-independent sweet taste of sugars.

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Section: Discussionmentioning

confidence: 99%

“…1). The Tas1r3 gene encoding T1r3 is allelic to Sac (2-7), the major genetic determinant of saccharin and sugar preference in inbred mice (8)(9)(10). KO mice deficient in either Tas1r2 or Tas1r3 display profound deficits in their responses to sweeteners (11,12).…”

mentioning

confidence: 99%

Glucose transporters and ATP-gated K ⁺ (K _ATP ) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells

Yee

Sukumaran

Kotha

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

189

178

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“…An additional advantage to allowing mice 4 days to consume each solution is that recent work indicated that two-bottle choice tests (conducted across a range of 1 -6 days) were most sensitive to detect strain differences when they lasted 4 days (Tordoff and Bachmanov, 2002). The 0.2% saccharin solution was chosen based on early work indicating that it is the maximally preferred concentration for both the B6 and D2 inbred strains (Fuller, 1974). Additional goals were to: 1) Estimate the coefficient of genetic determination (or heritability) for these consumption traits (i.e., the proportion of observed variability that is genetically determined); 2) Examine genetic correlations, or the degree to which two phenotypes show common genetic influence, across other ethanol-related behaviors and archived data; and 3) Identify strains that exhibit very high or very low ethanol consumption.…”

Section: Introductionmentioning

confidence: 99%

Voluntary ethanol consumption in 22 inbred mouse strains

Yoneyama

Crabbe

Ford

et al. 2008

Alcohol

273

269

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Inbred strains are genetically stable across time and laboratories, allowing scientists to accumulate a record of phenotypes, including physiological characteristics and behaviors. To date, the C57/C58 family of inbred mouse strains has been identified as having the highest innate ethanol consumption, but some lineages have rarely or never been surveyed. Thus, the purpose of the present experiment was to measure ethanol preference and intake in 22 inbred mouse strains, some of which have never been tested for ethanol consumption. Male and female mice (A/J, BALB/cByJ, BTBR+T tf/tf , BUB/ BnJ, C57BL/6J, C57BLKS/J, C58/J, CZECH/Ei, DBA/2J, FVB/NJ, I/LnJ, LP/J, MA/MyJ, NOD/ LtJ, NON/LtJ, NZB/B1NJ, NZW/LacJ, PERA/Ei, RIIIS/J, SEA/GnJ, SM/J, and 129S1/SvlmJ) were individually housed and given unlimited access in a two-bottle choice procedure to one bottle containing tap water and a second containing increasing concentrations of ethanol (3%, 6%, 10%), 0.2% saccharin, and then increasing concentrations of ethanol (3%, 6%, 10%) plus 0.2% saccharin. Mice were given access to each novel solution for a total of 4 days, with a bottle side change every other day. Consistent with previous studies, C57BL/6J (B6) mice consumed an ethanol dose of > 10g/kg/day while DBA/2J (D2) mice consumed < 2g/kg/day. No strain voluntarily consumed greater doses of ethanol than B6 mice. While the C58 and C57BLKS strains showed high ethanol consumption levels that were comparable to B6 mice, the BUB and BTBR strains exhibited low ethanol intakes similar to D2 mice. The addition of 0.2% saccharin to the ethanol solutions significantly increased ethanol intake by most strains and altered the strain distribution pattern. Strong positive correlations (rs ≥ 0.83) were determined between consumption of the unsweetened versus sweetened ethanol solutions. Consumption of saccharin alone was significantly positively correlated with the sweetened ethanol solutions (rs = 0.62 -0.81), but the correlation with unsweetened ethanol solutions was considerably lower (rs = 0.37 -0.45). These results add new strains to the strain mean database that will facilitate the identification of genetic relationships between voluntary ethanol consumption, saccharin preference, and other phenotypes.

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“…Fuller (1974) demonstrated that most of the differences in saccharin preferences between C57BL/6J and DBA/2J strains depend on a single locus, Sac, with the dominant Sac b allele present in the C57BL/6J strain. Subsequent studies confirmed this finding in the BXD recombinant inbred strains, in crosses between the C57BL/6 and DBA/2 strains (Lush, 1989;Belknap et al, 1992;Phillips et al, 1994;Lush et al, 1995;Blizard et al, 1999) and in crosses between the C57BL/6ByJ and 129P3/J strains (Bachmanov et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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

Reed

Li²,

Li³

et al. 2004

J. Neurosci.

164

146

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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.

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Single-Locus Control of Saccharin Preference in Mice

Cited by 158 publications

References 7 publications

Glucose transporters and ATP-gated K ⁺ (K _ATP ) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells

Glucose transporters and ATP-gated K ⁺ (K _ATP ) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells

Voluntary ethanol consumption in 22 inbred mouse strains

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

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Single-Locus Control of Saccharin Preference in Mice

Cited by 158 publications

References 7 publications

Glucose transporters and ATP-gated K + (K ATP ) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells

Glucose transporters and ATP-gated K + (K ATP ) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells

Voluntary ethanol consumption in 22 inbred mouse strains

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

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Product

Resources

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Glucose transporters and ATP-gated K ⁺ (K _ATP ) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells

Glucose transporters and ATP-gated K ⁺ (K _ATP ) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells