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

Calcium and magnesium are essential for survival but it is unknown how animals detect and consume enough of these minerals to meet their needs. To investigate this, we exploited the PWK/PhJ (PWK) strain of mice, which, in contrast to the C57BL/6J (B6) and other inbred strains, displays strong preferences for calcium solutions. We found that the PWK strain also has strong preferences for MgCl2 and saccharin solutions but not representative salty, sour, bitter, or umami taste compounds. A genome scan of B6 × PWK F2 mice linked a component of the strain difference in calcium and magnesium preference to distal chromosome 4. The taste receptor gene, Tas1r3, was implicated by studies with 129.B6ByJ- Tas1r3 congenic and Tas1r3 knockout mice. Most notably, calcium and magnesium solutions that were avoided by wild-type B6 mice were preferred (relative to water) by B6 mice null for the Tas1r3 gene. Oral calcium elicited less electrophysiological activity in the chorda tympani nerve of Tas1r3 knockout than wild-type mice. Comparison of the sequence of Tas1r3 with calcium and saccharin preferences in inbred mouse strains found 1) an inverse correlation between calcium and saccharin preference scores across primarily domesticus strains, which was associated with an I60T substitution in T1R3, and 2) a V689A substitution in T1R3 that was unique to the PWK strain and thus may be responsible for its strong calcium and magnesium preference. Our results imply that, in addition to its established roles in the detection of sweet and umami compounds, T1R3 functions as a gustatory calcium-magnesium receptor.

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Faculty Opinions recommendation of Gustatory expression pattern of the human TAS2R bitter receptor gene family reveals a heterogenous population of bitter responsive taste receptor cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1098163.554164 ◽

2007 ◽

Author(s):

Sue Kinnamon

Keyword(s):

Gene Family ◽

Expression Pattern ◽

Receptor Gene ◽

Taste Receptor ◽

Receptor Cells ◽

Heterogenous Population ◽

Taste Receptor Cells ◽

Receptor Gene Family

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Positive Darwinian selection in the singularly large taste receptor gene family of an ‘ancient’ fish, Latimeria chalumnae

BMC Genomics ◽

10.1186/1471-2164-15-650 ◽

2014 ◽

Vol 15 (1) ◽

pp. 650 ◽

Cited By ~ 17

Author(s):

Adnan S Syed ◽

Sigrun I Korsching

Keyword(s):

Gene Family ◽

Receptor Gene ◽

Taste Receptor ◽

Positive Darwinian Selection ◽

Darwinian Selection ◽

Latimeria Chalumnae ◽

Receptor Gene Family

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Molecular Identification of a Taste Receptor Gene for Trehalose in Drosophila

Science ◽

10.1126/science.289.5476.116 ◽

2000 ◽

Vol 289 (5476) ◽

pp. 116-119 ◽

Cited By ~ 34

Author(s):

H. Ishimoto

Keyword(s):

Molecular Identification ◽

Receptor Gene ◽

Taste Receptor

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Variation in the Bitter-taste Receptor Gene TAS2R38 , and Adiposity in a Genetically Isolated Population in Southern Italy

Obesity ◽

10.1038/oby.2008.357 ◽

2008 ◽

Vol 16 (10) ◽

pp. 2289-2295 ◽

Cited By ~ 117

Author(s):

Beverly J. Tepper ◽

Yvonne Koelliker ◽

Liqiang Zhao ◽

Natalia V. Ullrich ◽

Carmela Lanzara ◽

...

Keyword(s):

Southern Italy ◽

Bitter Taste ◽

Receptor Gene ◽

Taste Receptor ◽

Isolated Population ◽

Bitter Taste Receptor ◽

Bitter Taste Receptor Gene

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Genetics of sweet taste preferences

Pure and Applied Chemistry ◽

10.1351/pac200274071135 ◽

2002 ◽

Vol 74 (7) ◽

pp. 1135-1140 ◽

Cited By ~ 15

Author(s):

Alexander A. Bachmanov ◽

Danielle R. Reed ◽

Xia Li ◽

Gary K. Beauchamp

Keyword(s):

Positional Cloning ◽

Inbred Mouse ◽

Taste Receptor ◽

Sweet Taste ◽

Mouse Strains ◽

Taste Receptors ◽

Chromosome 4 ◽

Sweet Taste Receptor ◽

Distal Chromosome ◽

Allelic Differences

Inbred mouse strains display marked differences in avidity for sweet solutions due in part to genetic differences among strains. Using several techniques, we have located a number of regions throughout the genome that influence sweetener acceptance. One prominent locus regulating differences in sweetener preferences among mouse strains is the saccharin preference (Sac) locus on distal chromosome 4. Afferent responses of gustatory nerves to sweeteners also vary as a function of allelic differences in the Sac locus, suggesting that this gene may encode a sweet taste receptor. Using a positional cloning approach, we identified a gene (Tas1r3) encoding the third member of the T1R family of putative taste receptors, T1R3. Introgression by serial back-crossing of a chromosomal fragment containing the Tas1r3 allele from the high sweetener-preferring strain onto the genetic background of the low sweetener-preferring strain rescued its low sweetener-preference phenotype. Tas1r3 has two common haplotypes, one found in mouse strains with elevated sweetener preference and the other in strains relatively indifferent to sweeteners. This study, in conjunction with complimentary recent studies from other laboratories, provides compelling evidence that Tas1r3 is equivalent to the Sac locus and that the T1R3 receptor (when co-expressed with taste receptor T1R2) responds to sweeteners. However, other sweetness receptors may remain to be identified.

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Diet Shapes the Evolution of the Vertebrate Bitter Taste Receptor Gene Repertoire

Molecular Biology and Evolution ◽

10.1093/molbev/mst219 ◽

2013 ◽

Vol 31 (2) ◽

pp. 303-309 ◽

Cited By ~ 91

Author(s):

Diyan Li ◽

Jianzhi Zhang

Keyword(s):

Bitter Taste ◽

Receptor Gene ◽

Taste Receptor ◽

Gene Repertoire ◽

Bitter Taste Receptor ◽

Bitter Taste Receptor Gene

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New Insights on the Evolution of the Sweet Taste Receptor of Primates Adapted to Harsh Environments

Animals ◽

10.3390/ani10122359 ◽

2020 ◽

Vol 10 (12) ◽

pp. 2359

Author(s):

Nur Aida Md Tamrin ◽

Ramlah Zainudin ◽

Yuzine Esa ◽

Halimah Alias ◽

Mohd Noor Mat Isa ◽

...

Keyword(s):

Phylogenetic Trees ◽

Environmental Changes ◽

Receptor Gene ◽

Taste Receptor ◽

Sensory Information ◽

Sweet Taste ◽

Taste Perception ◽

Sweet Taste Receptor ◽

Dietary Preferences ◽

Starting Point

Taste perception is an essential function that provides valuable dietary and sensory information, which is crucial for the survival of animals. Studies into the evolution of the sweet taste receptor gene (TAS1R2) are scarce, especially for Bornean endemic primates such as Nasalis larvatus (proboscis monkey), Pongo pygmaeus (Bornean orangutan), and Hylobates muelleri (Muller’s Bornean gibbon). Primates are the perfect taxa to study as they are diverse dietary feeders, comprising specialist folivores, frugivores, gummivores, herbivores, and omnivores. We constructed phylogenetic trees of the TAS1R2 gene for 20 species of anthropoid primates using four different methods (neighbor-joining, maximum parsimony, maximum-likelihood, and Bayesian) and also established the time divergence of the phylogeny. The phylogeny successfully separated the primates into their taxonomic groups as well as by their dietary preferences. Of note, the reviewed time of divergence estimation for the primate speciation pattern in this study was more recent than the previously published estimates. It is believed that this difference may be due to environmental changes, such as food scarcity and climate change, during the late Miocene epoch, which forced primates to change their dietary preferences. These findings provide a starting point for further investigation.

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Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.

Journal of Experimental Medicine ◽

10.1084/jem.171.5.1665 ◽

1990 ◽

Vol 171 (5) ◽

pp. 1665-1681 ◽

Cited By ~ 12

Author(s):

F Falcioni ◽

Z Dembic ◽

S Muller ◽

P V Lehmann ◽

Z A Nagy

Keyword(s):

T Cell ◽

Receptor Gene ◽

Bovine Insulin ◽

Mouse Strains ◽

Specific Response ◽

T Cell Repertoire ◽

Cell Repertoire ◽

Fine Specificity ◽

Self Tolerance ◽

Gene Usage

Bovine insulin(BI)-specific I-Ab-restricted T cell clones have been characterized for fine specificity and TCR gene usage. We have demonstrated that mouse strains carrying H-2b on three different genetic backgrounds (C57BL, BALB, and 129) rearrange and express the V beta 6 gene in a large proportion (36%) of insulin-specific clones. In these strains, the non-MHC background did not seem to influence TCR gene usage in response to BI. The V beta 6+ clones appeared to be selected by the antigen. In contrast, no V beta 6+ clones could be isolated from (B6 x DBA/2)F1 mice, where V beta 6+ (and V beta 8.1+) T cells are deleted by self tolerance to Mls-1a. Thus, although a small proportion of residual V beta 6+ cells had been demonstrated in Mls-1a mice, these cells could not be retrieved in a response that uses V beta 6 predominantly. In functional terms, therefore, the deletion of V beta 6 by self tolerance appears to be complete. Instead of V beta 6, the majority (up to 60%) of I-Ab- as well as I-Ad-restricted insulin-specific clones from the (B6 x DBA/2)F1 mice expressed V beta 8.2 and V beta 8.3. This shift of gene usage was not accompanied by any detectable change in the fine specificity pattern of response. Thus, in the insulin-specific response, the flexibility of T cell repertoire fully compensates for deletions caused by self tolerance.

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