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The Journal of Neuroscience, March 3, 2004, 24(9):2296-2303; doi:10.1523/JNEUROSCI.4439-03.2004

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Behavioral/Systems/Cognitive
Allelic Variation of the Tas1r3 Taste Receptor Gene Selectively Affects Behavioral and Neural Taste Responses to Sweeteners in the F₂ Hybrids between C57BL/6ByJ and 129P3/J Mice

Masashi Inoue,¹ Danielle R. Reed,² Xia Li,² Michael G. Tordoff,² Gary K. Beauchamp,^2,3 and Alexander A. Bachmanov²

¹Laboratory of Cellular Neurobiology, School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan, ²Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, and ³Department of Psychology and School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Recent studies have shown that the T1R3 receptor protein encoded by the Tas1r3 gene is involved in transduction of sweet taste. To assess ligand specificity of the T1R3 receptor, we analyzed the association of Tas1r3 allelic variants with taste responses in mice. In the F₂ hybrids between the C57BL/6ByJ (B6) and 129P3/J (129) inbred mouse strains, we determined genotypes of markers on chromosome 4, where Tas1r3 resides, measured consumption of taste solutions presented in two-bottle preference tests, and recorded integrated responses of the chorda tympani gustatory nerve to lingual application of taste stimuli. For intakes and preferences, significant linkages to Tas1r3 were found for the sweeteners sucrose, saccharin, and D-phenylalanine but not glycine. For chorda tympani responses, significant linkages to Tas1r3 were found for the sweeteners sucrose, saccharin, D-phenylalanine, D-tryptophan, and SC-45647 but not glycine, L-proline, L-alanine, or L-glutamine. No linkages to distal chromosome 4 were detected for behavioral or neural responses to non-sweet quinine, citric acid, HCl, NaCl, KCl, monosodium glutamate, inosine 5'-monophosphate, or ammonium glutamate. These results demonstrate that allelic variation of the Tas1r3 gene affects gustatory neural and behavioral responses to some, but not all, sweeteners. This study describes the range of ligand sensitivity of the T1R3 receptor using an in vivo approach and, to our knowledge, is the first genetic mapping study of activity in gustatory nerves.

Key words: taste; sweet; preference; consumption; chorda tympani nerve; electrophysiology; genetics

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Received Sep 30, 2003; revised January 6, 2004; accepted January 7, 2004.

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