Single-locus control of saccharin intake in BXD/Ty recombinant inbred (RI) mice: Some methodological implications for RI strain analysis

Belknap, John K.; Crabbe, John C.; Plomin, Robert; McClearn, Gerald E.; Sampson, K. E.; O’Toole, L. A.; Gora-Maslak, Grazyna

doi:10.1007/bf01066794

Cited by 58 publications

(27 citation statements)

References 14 publications

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“…In 1974, using long-term two-bottle tests, Fuller (60) showed that differences in saccharin preferences between the C57BL/6 and DBA/2 inbred strains largely depend on a single locus, Sac, with a dominant Sac b allele present in the C57BL/6 strain that was associated with higher saccharin preference and a recessive Sac d allele present in the DBA/2 strain that was associated with lower saccharin preference. Subsequent studies confirmed this finding in the BXD recombinant inbred strains, and in crosses between the C57BL/6 and DBA/2 and between the C57BL/6 and 129 strains (16,23,26,113,115,133). In addition to sweetener preferences, the Sac genotype influenced the afferent responses of gustatory nerves to sweeteners (16,98), which indicated that the Sac gene is involved in peripheral taste transduction and may encode a sweet taste receptor.…”

Section: T1r Receptors Discoverysupporting

confidence: 62%

Taste Receptor Genes

Bachmanov

Beauchamp²

2007

Annu. Rev. Nutr.

386

381

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In the past several years, tremendous progress has been achieved with the discovery and characterization of vertebrate taste receptors from the T1R and T2R families, which are involved in recognition of bitter, sweet, and umami taste stimuli. Individual differences in taste, at least in some cases, can be attributed to allelic variants of the T1R and T2R genes. Progress with understanding how T1R and T2R receptors interact with taste stimuli and with identifying their patterns of expression in taste cells sheds light on coding of taste information by the nervous system. Candidate mechanisms for detection of salts, acids, fat, complex carbohydrates, and water have also been proposed, but further studies are needed to prove their identity.

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Section: T1r Receptors Discoverysupporting

confidence: 62%

Taste Receptor Genes

Bachmanov

Beauchamp²

2007

Annu. Rev. Nutr.

386

381

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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). The Sac locus has been mapped to the subtelomeric region of mouse chromosome 4 (Phillips et al, 1994;Lush et al, 1995;Bachmanov et al, 1997;Blizard et al, 1999;Li et al, 2001) and more recently has been cloned positionally .…”

Section: Introductionsupporting

confidence: 58%

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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Section: Discussionmentioning

confidence: 81%

“…Although there still may have been interactions between solutions tested in this study, it seems unlikely that they would be sufficiently robust to affect the main conclusions about the direction of strain differences between B6 and 129 strains. Indeed, in our other experiments on these strains, 9,20,30 as well as in studies by other authors, 5,8,[10][11][12]15 B6 and 129 mice had the same character of differences in ethanol, sucrose, saccharin, citric acid, quinine, and NaCl consumption, regardless of whether the solutions were tested in the same or in different groups of animals.To summarize, the higher ethanol consumption of B6 mice relative to 129 mice is accompanied by higher preferences for sweet and sour, possible reduction in the aversion to bitter, no change in capsaicin sensitivity, and a lower preference for salty taste. These data are consistent with the hypothesis that the higher ethanol intake by B6 mice depends, in part, on higher hedonic attractiveness of its sweet taste component.…”

mentioning

confidence: 81%

Ethanol Consumption and Taste Preferences in C57BL/6ByJ and 129/J Mice

Bachmanov

Tordoff

Beauchamp

1996

Alcoholism Clin & Exp Res

155

124

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Mice of the C57BL/6ByJ (B6) and 129/J (129) strains were offered different concentrations of taste solutions in 48-hr, two-bottle choice tests. In comparison with the 129 strain, the B6 strain had higher preferences for ethanol, sucrose, and citric acid. They had lower preferences for NaCI and similar preferences for capsaicin and quinine hydrochloride. These data are consistent with the hypothesis that the higher ethanol intake by B6 mice depends, in part, on higher hedonic attractiveness of its sweet taste component. KeywordsMouse Strains; Ethanol Consumption; Taste Preference.IN RODENTS, the volume of ethanol consumed depends in part on its flavor, 1 but the relationship between intake and flavor is not well understood. A sweet component to alcohol taste has been demonstrated in rats, 2 which is consistent with several studies showing that the proclivity to drink alcohol is associated with elevated sweet preferences. [3][4][5] However, alcohol intake is also associated with reduced NaCI preferences, 4,6 even though it is not considered salty, and is unrelated to ingestion of bitter solutions 4 despite being bitter. 2 In addition to its gustatory properties, alcohol activates the olfactory and trigeminal (irritation/ burn) systems, 7 but there is no work to determine whether these are related to differences in intake.The goal of the present study was to characterize the relationships between genetically determined differences in ethanol consumption and perception of the four main taste qualities and burning sensation. For this purpose, preferences for various concentrations of ethanol, sucrose, citric acid, quinine, NaCI, and capsaicin were tested in mice of C57BL/ 6ByJ (B6) and 129/J (129) strains. The B6 and 129 mouse strains were chosen because in previous studies they revealed differences in ethanol intake, 5 as well as in preferences for sweet and salty substances. 5,8,9 Because few data are available concerning taste acceptance in the 129 strain, it seemed important to test animals with a range of taste solutions. Another reason for testing the 129/J strain was that the closely related 129/SvJ strain is commonly used for transgenic studies. Thus, the results found herein could potentially provide relevant background data for studies examining taste preferences in transgenic mice. Copyright © 1996 METHODS SubjectsMale B6 and the 129 mice were obtained from The Jackson Laboratory (Bar Harbor, ME). The mice were housed in individual cages in a temperature-controlled room at 23°C on a 12-hr light/dark cycle. They had free access to water and Teklad Rodent Diet 8604.Ethanol, sucrose, citric acid, quinine, and capsaicin were tested using eight B6 mice and twelve 129 mice. Before the experiments described in this study, the mice were used in another study that involved noninvasive measurements of 75 to 300 mM NaCI solution intake and sodium excretion. Preference measurements started when the animals were 6.5 to 7 months old, and their weight was 32.1 ± 1.0 g (B6) and 28.6 ± 0.5 g (129). After ethanol...

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Single-locus control of saccharin intake in BXD/Ty recombinant inbred (RI) mice: Some methodological implications for RI strain analysis

Cited by 58 publications

References 14 publications

Taste Receptor Genes

Taste Receptor Genes

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

Ethanol Consumption and Taste Preferences in C57BL/6ByJ and 129/J Mice

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