Genetics of mouse behavioral and peripheral neural responses to sucrose.

Mice of the C57BL/6ByJ (B6) strain have higher consumption of sucrose, and stronger peripheral neural responses to it, than do mice of the 129P3/J (129) strain. To identify quantitative trait loci (QTLs) responsible for this strain difference and to evaluate the contribution of peripheral taste responsiveness to individual differences in sucrose intake, we produced an intercross (F) of 627 mice, measured their sucrose consumption in two-bottle choice tests, recorded the electrophysiological activity of the chorda tympani nerve elicited by sucrose in a subset of F mice, and genotyped the mice with DNA markers distributed in every mouse chromosome. We confirmed a sucrose consumption QTL (Scon2, or Sac) on mouse chromosome (Chr) 4, harboring the Tas1r3 gene, which encodes the sweet taste receptor subunit TAS1R3 and affects both behavioral and neural responses to sucrose.

Burly1 is a mouse QTL for lean body mass that maps to a 0.8-Mb region of chromosome 2.

To fine map a mouse QTL for lean body mass (Burly1), we used information from intercross, backcross, consomic, and congenic mice derived from the C57BL/6ByJ (host) and 129P3/J (donor) strains. The results from these mapping populations were concordant and showed that Burly1 is located between 151.9 and 152.

Adiposity QTL Adip20 decomposes into at least four loci when dissected using congenic strains.

An average mouse in midlife weighs between 25 and 30 g, with about a gram of tissue in the largest adipose depot (gonadal), and the weight of this depot differs between inbred strains. Specifically, C57BL/6ByJ mice have heavier gonadal depots on average than do 129P3/J mice. To understand the genetic contributions to this trait, we mapped several quantitative trait loci (QTLs) for gonadal depot weight in an F2 intercross population.

Arginyl dipeptides increase the frequency of NaCl-elicited responses via epithelial sodium channel alpha and delta subunits in cultured human fungiform taste papillae cells.

Salty taste is one of the five basic tastes and is often elicited by NaCl. Because excess sodium intake is associated with many health problems, it could be useful to have salt taste enhancers that are not sodium based. In this study, the regulation of NaCl-induced responses was investigated in cultured human fungiform taste papillae (HBO) cells with five arginyl dipeptides: Ala-Arg (AR), Arg-Ala (RA), Arg-Pro (RP), Arg-Glu (RE), and Glu-Arg (ER); and two non-arginyl dipeptides: Asp-Asp (DD) and Glu-Asp (ED).

Whole transcriptome profiling of taste bud cells.

Analysis of single-cell RNA-Seq data can provide insights into the specific functions of individual cell types that compose complex tissues. Here, we examined gene expression in two distinct subpopulations of mouse taste cells: Tas1r3-expressing type II cells and physiologically identified type III cells. Our RNA-Seq libraries met high quality control standards and accurately captured differential expression of marker genes for type II (e.

Genetics of Amino Acid Taste and Appetite.

The consumption of amino acids by animals is controlled by both oral and postoral mechanisms. We used a genetic approach to investigate these mechanisms. Our studies have shown that inbred mouse strains differ in voluntary amino acid consumption, and these differences depend on sensory and nutritive properties of amino acids.

Amiloride-Insensitive Salt Taste Is Mediated by Two Populations of Type III Taste Cells with Distinct Transduction Mechanisms.

Unlabelled: Responses in the amiloride-insensitive (AI) pathway, one of the two pathways mediating salty taste in mammals, are modulated by the size of the anion of a salt. This "anion effect" has been hypothesized to result from inhibitory transepithelial potentials (TPs) generated across the lingual epithelium as cations permeate through tight junctions and leave their larger and less permeable anions behind (Ye et al., 1991).

Body Composition QTLs Identified in Intercross Populations Are Reproducible in Consomic Mouse Strains.

Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity.

Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein.

Regulation of bitter taste responses by tumor necrosis factor.

Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake.

Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo.

Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its homologs (e.g., Lgr6) mark adult stem cells in multiple tissues.

Skn-1a/Pou2f3 is required for the generation of Trpm5-expressing microvillous cells in the mouse main olfactory epithelium.

Background: The main olfactory epithelium (MOE) in mammals is a specialized organ to detect odorous molecules in the external environment. The MOE consists of four types of cells: olfactory sensory neurons, supporting cells, basal cells, and microvillous cells. Among these, development and function of microvillous cells remain largely unknown.

Pou2f3/Skn-1a is necessary for the generation or differentiation of solitary chemosensory cells in the anterior nasal cavity.

Solitary chemosensory cells in the non-neuronal epithelium of the anterior nasal cavity have bitter taste cell-like molecular characteristics and are involved in the detection of noxious substances. Here, we demonstrate that Pou2f3/Skn-1a, which is necessary for generation of sweet, umami, and bitter taste cells, is also necessary for the generation or differentiation of solitary chemosensory cells.

QTL analysis of dietary obesity in C57BL/6byj X 129P3/J F2 mice: diet- and sex-dependent effects.

Obesity is a heritable trait caused by complex interactions between genes and environment, including diet. Gene-by-diet interactions are difficult to study in humans because the human diet is hard to control. Here, we used mice to study dietary obesity genes, by four methods.

Genetics of taste receptors.

Taste receptors function as one of the interfaces between internal and external milieus. Taste receptors for sweet and umami (T1R [taste receptor, type 1]), bitter (T2R [taste receptor, type 2]), and salty (ENaC [epithelial sodium channel]) have been discovered in the recent years, but transduction mechanisms of sour taste and ENaC-independent salt taste are still poorly understood. In addition to these five main taste qualities, the taste system detects such noncanonical "tastes" as water, fat, and complex carbohydrates, but their reception mechanisms require further research.

A/J and C57BL/6J mice differ in chorda tympani responses to NaCl.

The molecular mechanisms of sodium taste transduction are not completely understood, especially those responsible for the portion of NaCl's taste in rodents that is not blocked by amiloride. As a prelude to conducting genetic analyses of peripheral NaCl taste responsiveness, we performed multiunit electrophysiological recordings from the chorda tympani (CT) nerve in C57BL/6J (B6) and A/J mice. Mice were anesthetized, the CT was accessed, and taste solutions were flowed over the tongue in order to measure the integrated whole-nerve response.

Genetic analysis of chemosensory traits in human twins.

We explored genetic influences on the perception of taste and smell stimuli. Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride, citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium chloride, calcium chloride, cinnamon, androstenone, Galaxolide™, cilantro, and basil. For most traits, individual differences were stable over time and some traits were heritable (h(2) from 0.

Defects in the peripheral taste structure and function in the MRL/lpr mouse model of autoimmune disease.

While our understanding of the molecular and cellular aspects of taste reception and signaling continues to improve, the aberrations in these processes that lead to taste dysfunction remain largely unexplored. Abnormalities in taste can develop in a variety of diseases, including infections and autoimmune disorders. In this study, we used a mouse model of autoimmune disease to investigate the underlying mechanisms of taste disorders.

NaCl taste thresholds in 13 inbred mouse strains.

Molecular mechanisms of salty taste in mammals are not completely understood. We use genetic approaches to study these mechanisms. Previously, we developed a high-throughput procedure to measure NaCl taste thresholds, which involves conditioning mice to avoid LiCl and then examining avoidance of NaCl solutions presented in 48-h 2-bottle preference tests.

Genetics of sweet taste preferences.

Sweet taste is a powerful factor influencing food acceptance. There is considerable variation in sweet taste perception and preferences within and among species. Although learning and homeostatic mechanisms contribute to this variation in sweet taste, much of it is genetically determined.

Effect of chorda tympani nerve transection on salt taste perception in mice.

Effects of gustatory nerve transection on salt taste have been studied extensively in rats and hamsters but have not been well explored in the mouse. We examined the effects of chorda tympani (CT) nerve transection on NaCl taste preferences and thresholds in outbred CD-1 mice using a high-throughput phenotyping method developed in our laboratory. To measure taste thresholds, mice were conditioned by oral self-administration of LiCl or NaCl and then presented with NaCl concentration series in 2-bottle preference tests.

Sweet taste receptor gene variation and aspartame taste in primates and other species.

Aspartame is a sweetener added to foods and beverages as a low-calorie sugar replacement. Unlike sugars, which are apparently perceived as sweet and desirable by a range of mammals, the ability to taste aspartame varies, with humans, apes, and Old World monkeys perceiving aspartame as sweet but not other primate species. To investigate whether the ability to perceive the sweetness of aspartame correlates with variations in the DNA sequence of the genes encoding sweet taste receptor proteins, T1R2 and T1R3, we sequenced these genes in 9 aspartame taster and nontaster primate species.

Bitter avoidance in guinea pigs (Cavia porcellus) and mice (Mus musculus and Peromyscus leucopus).

Rejection of bitter substances is common in many species and may function to protect an animal from ingestion of bitter-tasting toxins. Since many plants are bitter, it has been proposed that high tolerance for bitterness would be adaptive for herbivores. Earlier studies conducted on herbivorous guinea pigs (Cavia porcellus) have been used to support this proposal.

Taste function in mice with a targeted mutation of the pkd1l3 gene.

Recent studies, both in vitro and in vivo, have suggested the involvement of the polycystic kidney disease-1 and -2 like genes, Pkd1l3 and Pkd2l1, in acid taste transduction. In mice, disruption of taste cells expressing PKD2L1 eliminates gustatory neural responses to acids. However, no previous data exist on taste responses in the absence of PKD1L3 or on behavioral responses in mice lacking either of these proteins.