scholarly journals Genetic controls of mouse Tas1r3-independent sucrose intake

2018 ◽  
Author(s):  
Cailu Lin ◽  
Michael G. Tordoff ◽  
Xia Li ◽  
Natalia P. Bosak ◽  
Masashi Inoue ◽  
...  
Keyword(s):  
Inbred Mouse ◽  
Taste Receptor ◽  
Chromosome Mapping ◽  
Sweet Taste ◽  
Mouse Strains ◽  
Sucrose Intake ◽  
Glucose Homoeostasis ◽  
Insulin Tolerance ◽  
Gustatory Nerve ◽  
Nerve Recordings

AbstractWe have previously shown that variation in sucrose intake among inbred mouse strains is due in part to polymorphisms in the Tas1r3 gene, which encodes a sweet taste receptor subunit and accounts for the Sac locus on distal Chr4. To discover other quantitative trait loci (QTLs) influencing sucrose intake, voluntary daily sucrose intake was measured in an F2 intercross with the Sac locus fixed; in backcross, reciprocal consomic strains; and in single- and double-congenic strains. Chromosome mapping identified Scon3, located on Chr9, and epistasis of Scon3 with Scon4 on Chr1. Mice with different combinations of Scon3 and Scon4 genotypes differed more than threefold in sucrose intake. To understand how these two QTLs influenced sucrose intake, we measured resting metabolism, glucose and insulin tolerance, and peripheral taste responsiveness in congenic mice. We found that the combinations of Scon3 and Scon4 genotypes influenced thermogenesis and the oxidation of fat and carbohydrate. Results of glucose and insulin tolerance tests, peripheral taste tests, and gustatory nerve recordings ruled out plasma glucose homoeostasis and peripheral taste sensitivity as major contributors to the differences in voluntary sucrose consumption. Our results provide evidence that these two novel QTLs influence mouse-to-mouse variation in sucrose intake and that both likely act through a common postoral mechanism.

scholarly journals Genetics of sweet taste preferences

2002 ◽  
Vol 74 (7) ◽  
pp. 1135-1140 ◽  
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.

scholarly journals T1R3 taste receptor is critical for sucrose but not Polycose taste

2009 ◽  
Vol 296 (4) ◽  
pp. R866-R876 ◽  
Author(s):  
Steven Zukerman ◽  
John I. Glendinning ◽  
Robert F. Margolskee ◽  
Anthony Sclafani
Keyword(s):  
Critical Role ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Sucrose Preference ◽  
Chorda Tympani ◽  
Chorda Tympani Nerve ◽  
Sweet Taste Receptor ◽  
Sucrose Solutions ◽  
Nerve Recordings

In addition to their well-known preference for sugars, mice and rats avidly consume starch-derived glucose polymers (e.g., Polycose). T1R3 is a component of the mammalian sweet taste receptor that mediates the preference for sugars and artificial sweeteners in mammals. We examined the role of the T1R3 receptor in the ingestive response of mice to Polycose and sucrose. In 60-s two-bottle tests, knockout (KO) mice preferred Polycose solutions (4–32%) to water, although their overall preference was lower than WT mice (82% vs. 94%). KO mice also preferred Polycose (0.5–32%) in 24-h two-bottle tests, although less so than WT mice at dilute concentrations (0.5–4%). In contrast, KO mice failed to prefer sucrose to water in 60-s tests. In 24-h tests, KO mice were indifferent to 0.5–8% sucrose, but preferred 16–32% sucrose; this latter result may reflect the post-oral effects of sucrose. Overall sucrose preference and intake were substantially less in KO mice than WT mice. However, when retested with 0.5–32% sucrose solutions, the KO mice preferred all sucrose concentrations, although they drank less sugar than WT mice. The experience-induced sucrose preference is attributed to a post-oral conditioned preference for the T1R3-independent orosensory features of the sugar solutions (odor, texture, T1R2-mediated taste). Chorda tympani nerve recordings revealed virtually no response to sucrose in KO mice, but a near-normal response to Polycose. These results indicate that the T1R3 receptor plays a critical role in the taste-mediated response to sucrose but not Polycose.

scholarly journals Involvement of T1R3 in calcium-magnesium taste

2008 ◽  
Vol 34 (3) ◽  
pp. 338-348 ◽  
Author(s):  
Michael G. Tordoff ◽  
Hongguang Shao ◽  
Laura K. Alarcón ◽  
Robert F. Margolskee ◽  
Bedrich Mosinger ◽  
...  
Keyword(s):  
Strain Difference ◽  
Receptor Gene ◽  
Inbred Mouse ◽  
Taste Receptor ◽  
Mouse Strains ◽  
Chorda Tympani Nerve ◽  
Wild Type ◽  
A Genome ◽  
Calcium Magnesium ◽  
Calcium And Magnesium

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.

scholarly journals T1R2+T1R3-independent chemosensory inputs contributing to behavioral discrimination of sugars in mice

2019 ◽  
Vol 316 (5) ◽  
pp. R448-R462 ◽  
Author(s):  
Lindsey A. Schier ◽  
Chizuko Inui-Yamamoto ◽  
Ginger D. Blonde ◽  
Alan C. Spector
Keyword(s):  
Neural Circuits ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Mouse Strains ◽  
Wild Type ◽  
Double Knockout ◽  
Sweet Taste Receptor ◽  
Rat Study ◽  
Behavioral Discrimination

Simple sugars are thought to elicit a unitary sensation, principally via the “sweet” taste receptor type 1 taste receptor (T1R)2+T1R3, yet we previously found that rats with experience consuming two metabolically distinct sugars, glucose and fructose, subsequently licked more for glucose than fructose, even when postingestive influences were abated. The results pointed to the existence of an orosensory receptor that binds one sugar but not the other and whose signal is channeled into neural circuits that motivate ingestion. Here we sought to determine the chemosensory nature of this signal. First, we assessed whether T1R2 and/or T1R3 are necessary to acquire this behavioral discrimination, replicating our rat study in T1R2+T1R3 double-knockout (KO) mice and their wild-type counterparts as well as in two common mouse strains that vary in their sensitivity to sweeteners [C57BL/6 (B6) and 129X1/SvJ (129)]. These studies showed that extensive exposure to multiple concentrations of glucose and fructose in daily one-bottle 30-min sessions enhanced lick responses for glucose over fructose in brief-access tests. This was true even for KO mice that lacked the canonical “sweet” taste receptor. Surgical disconnection of olfactory inputs to the forebrain (bulbotomy) in B6 mice severely disrupted the ability to express this experience-dependent sugar discrimination. Importantly, these bulbotomized B6 mice exhibited severely blunted responsiveness to both sugars relative to water in brief-access lick tests, despite the fact that they have intact T1R2+T1R3 receptors. The results highlight the importance of other sources of chemosensory and postingestive inputs in shaping and maintaining “hardwired” responses to sugar.

Tracking genetic variation underlying differenzial reaction to TGF-beta signalling in inbred mouse strains

2011 ◽  
Vol 49 (08) ◽  
Author(s):  
R Müllenbach ◽  
I Ilkavets ◽  
S Dooley ◽  
F Lammert
Keyword(s):  
Genetic Variation ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Tgf Beta

Effect of taste receptor protein T1R3 on the development of islet tissue of the murine pancreas

2019 ◽  
Vol 484 (1) ◽  
pp. 117-120
Author(s):  
V. O. Murovets ◽  
E. A. Sozontov ◽  
T. G. Zachepilo
Keyword(s):  
Parent Strain ◽  
Gene Knockout ◽  
Taste Receptor ◽  
Morphological Characteristics ◽  
Sweet Taste ◽  
Pancreatic Tissue ◽  
Receptor Protein ◽  
Gene Encoding ◽  
Islet Tissue ◽  
Knockout Animals

Protein T1R3, the main subunit of sweet, as well as amino acid, taste receptor, is expressed in the epithelium of the tongue and gastro intestinal tract, in β–cells of the pancreas, hypothalamus, and numerous other organs. Recently, convincing witnesses of T1R3 involvement in control of carbohydrate and lipid metabolism, and control of production of incretines and insulin, have been determined. In the study on Tas1r3-gene knockout mouse strain and parent strain C57Bl/6J as control, priority data concerning the effect of T1R3 on the morphological characteristics of Langerhans islets in the pancreas, are obtained. In Tas1r3 knockout animals, it is found that the size of the islets and their density in pancreatic tissue are reduced, as compared to the parent strain. Additionally, a decrease of expression of active caspase-3 in islets of gene-knockouts is demonstrated. The obtained data show that the lack of a functional, gene encoding sweet-taste receptor protein causes a dystrophy of the islet tissue and associates to the development of pathological changes in the pancreas specific to type-2 diabetes and obesity in humans.

scholarly journals POST-FERTILIZATION MATERNAL EFFECTS ON SPERM DIMENSIONS OF INBRED MOUSE STRAINS

Reproduction ◽  
1973 ◽  
Vol 33 (1) ◽  
pp. 175-177 ◽  
Author(s):  
K. P. PANT ◽  
R. A. BEATTY
Keyword(s):  
Maternal Effects ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains

scholarly journals Genetic Control of Mammalian Meiotic Recombination. I. Variation in Exchange Frequencies Among Males From Inbred Mouse Strains

Genetics ◽  
2002 ◽  
Vol 162 (1) ◽  
pp. 297-306 ◽  
Author(s):  
Kara E Koehler ◽  
Jonathan P Cherry ◽  
Audrey Lynn ◽  
Patricia A Hunt ◽  
Terry J Hassold
Keyword(s):  
Meiotic Recombination ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Male Meiosis ◽  
Mouse Strains ◽  
Recombination Rates ◽  
The Mean ◽  
Genetic Background Effects ◽  
Exchange Patterns ◽  
Positive Interference

AbstractGenetic background effects on the frequency of meiotic recombination have long been suspected in mice but never demonstrated in a systematic manner, especially in inbred strains. We used a recently described immunostaining technique to assess meiotic exchange patterns in male mice. We found that among four different inbred strains—CAST/Ei, A/J, C57BL/6, and SPRET/Ei—the mean number of meiotic exchanges per cell and, thus, the recombination rates in these genetic backgrounds were significantly different. These frequencies ranged from a low of 21.5 exchanges in CAST/Ei to a high of 24.9 in SPRET/Ei. We also found that, as expected, these crossover events were nonrandomly distributed and displayed positive interference. However, we found no evidence for significant differences in the patterns of crossover positioning between strains with different exchange frequencies. From our observations of >10,000 autosomal synaptonemal complexes, we conclude that achiasmate bivalents arise in the male mouse at a frequency of 0.1%. Thus, special mechanisms that segregate achiasmate chromosomes are unlikely to be an important component of mammalian male meiosis.

scholarly journals EVIDENCE THAT TWO LOCI PREDOMINANTLY DETERMINE THE DIFFERENCE IN SUSCEPTIBILITY TO THE HIGH PRESSURE NEUROLOGIC SYNDROME TYPE I SEIZURE IN MICE

Genetics ◽  
1981 ◽  
Vol 99 (2) ◽  
pp. 285-307
Author(s):  
R D McCall ◽  
D Frierson
Keyword(s):  
High Pressure ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Chromosome 17 ◽  
Seizure Threshold ◽  
Mouse Strains ◽  
Compression Rate ◽  
Type I ◽  
Major Locus ◽  
The Difference

ABSTRACT Most mammals tested, when exposed to increasing pressure in helium/oxygen atmospheres, exhibit progressive motor disturbances culminating in two, usually successive, well-differentiated convulsive seizures. The seizures are highly reproducible components of the constellation of events that collectively constitute the High Pressure Neurologic Syndrome (HPNS). In the present study, we present evidence that the mean difference in seizure threshold pressures of the first seizure to occur (HPNS Type I) between inbred mouse strains DBA/2J and C57BL/6J is predominantly determined (> 60%) by the expression of a major locus—possibly linked to the H-2 locus on chromosome 17—and a minor locus, probably unlinked. This outcome is derived from applications of the maximum likelihood modeling procedure of Elston and Stewart (1973) and Stewart and Elston (1973) to eleven models of genetic determinacy and tests (including breeding tests) of "preferred" models so derived using BXD recombinant inbred strains that show the following: The major locus exhibits conditional dominance characteristics depending upon compression rate and minor locus genotype. At a constant mean compression rate of 100 atm hr-1, the major locus manifests strong, though incomplete, dominance apparently independent of minor locus genotype. Its expression is, however, highly sensitive to compression rate, losing its dominance altogether at a linear rate of 1,000 atm hr-1. The major locus interacts with the weakly dominant and relatively compression-rate-insensitive minor locus to retain dominance at fast compression only when the dominant alleles of both loci are present. A principal finding of this study is that employing two compression rates permits fuller genetic characterization of murine high-pressure seizure susceptibility differences than could be achieved by use of a single compression rate.

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