The sense of taste is the primary sensory system that determines whether a food or beverage will be ingested or rejected. Taste also influences food processing by the digestive system. Consequently, understanding the mechanisms underlying this sense is central to our ability to control intake of nutrients and to modulate the excesses of consumption that may underlie diseases such as obesity, hypertension and the metabolic syndrome. Our approach to advancing understanding of taste perception has been to use mouse models to identify genes involved in perception. We first identify natural variation in behavioral responses to taste stimuli in inbred mouse strains and then use this information to locate and identify the genes responsible for this variation. This approach, sometimes called positional cloning, is capable of detecting genes involved in all stages of taste perception, from reception in taste bud cells to brain functions responsible for behavioral responses to taste stimuli. In our previous studies, which were the first successful use of positional cloning to identify a functional gene involved in mammalian behavior, we identified and characterized a locus that codes for a sweet taste receptor. In the current comprehensive proposal, we describe studies designed to continue to identify genes involved in behavioral responses to sweet compounds. We also propose to expand our scope to include sour taste-related genes. This positional cloning approach will be complemented with behavioral analyses of physiological mechanisms underlying effects of individual genes. These studies, when completed, may provide important new avenues for interventions designed to modify excess food consumption.

Public Health Relevance

The sense of taste is the primary sensory system that determines whether a food or beverage will be ingested or rejected. Consequently, understanding the mechanisms underlying this sense is central to our ability to control intake of nutrients and to modulate the excesses of consumption that may underlie diseases such as obesity, hypertension and the metabolic syndrome. We study the taste mechanisms using mouse as a model organism. Our approach, sometimes called positional cloning, is based on chromosomal mapping of genes responsible for variation in taste responsiveness. Previously, we used this approach to identify a locus that codes for a sweet taste receptor. In the current comprehensive proposal, we describe studies designed to continue to identify genes involved in sweet taste. We also propose to expand our scope to include sour taste- related genes. These studies, when completed, may provide important new avenues for interventions designed to modify excess food consumption.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
3R01DC000882-29S1
Application #
8672787
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
1983-08-01
Project End
2014-08-31
Budget Start
2013-06-15
Budget End
2014-08-31
Support Year
29
Fiscal Year
2013
Total Cost
$6,395
Indirect Cost
$2,068
Name
Monell Chemical Senses Center
Department
Type
DUNS #
088812565
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Lewandowski, Brian C; Sukumaran, Sunil K; Margolskee, Robert F et al. (2016) Amiloride-Insensitive Salt Taste Is Mediated by Two Populations of Type III Taste Cells with Distinct Transduction Mechanisms. J Neurosci 36:1942-53
Beauchamp, Gary K (2016) Why do we like sweet taste: A bitter tale? Physiol Behav 164:432-7
Murovets, Vladimir O; Bachmanov, Alexander A; Zolotarev, Vasiliy A (2015) Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene. PLoS One 10:e0130997
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Lin, Cailu; Fesi, Brad D; Marquis, Michael et al. (2015) Body Composition QTLs Identified in Intercross Populations Are Reproducible in Consomic Mouse Strains. PLoS One 10:e0141494
Bachmanov, Alexander A; Bosak, Natalia P; Lin, Cailu et al. (2014) Genetics of taste receptors. Curr Pharm Des 20:2669-83
Ren, Wenwen; Lewandowski, Brian C; Watson, Jaime et al. (2014) Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo. Proc Natl Acad Sci U S A 111:16401-6
Yamaguchi, Tatsuya; Yamashita, Junpei; Ohmoto, Makoto et al. (2014) Skn-1a/Pou2f3 is required for the generation of Trpm5-expressing microvillous cells in the mouse main olfactory epithelium. BMC Neurosci 15:13
Murovets, V O; Bachmanov, A A; Travnikov, S V et al. (2014) The Involvement of the T1R3 Receptor Protein in the Control of Glucose Metabolism in Mice at Different Levels of Glycemia. J Evol Biochem Physiol 50:334-344

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