Inoue Masashi, Reed Danielle R, Li Xia, Tordoff Michael G, Beauchamp Gary K, Bachmanov Alexander A
Laboratory of Cellular Neurobiology, School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan.
J Neurosci. 2004 Mar 3;24(9):2296-303. doi: 10.1523/JNEUROSCI.4439-03.2004.
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.
最近的研究表明,由Tas1r3基因编码的T1R3受体蛋白参与甜味转导。为了评估T1R3受体的配体特异性,我们分析了Tas1r3等位基因变体与小鼠味觉反应的关联。在C57BL/6ByJ(B6)和129P3/J(129)近交系小鼠品系之间的F2杂种中,我们确定了Tas1r3所在的4号染色体上标记的基因型,测量了两瓶偏好试验中呈现的味觉溶液的消耗量,并记录了鼓索味觉神经对舌部施加味觉刺激的综合反应。对于摄入量和偏好,发现甜味剂蔗糖、糖精和D-苯丙氨酸与Tas1r3有显著连锁,但甘氨酸没有。对于鼓索反应,发现甜味剂蔗糖、糖精、D-苯丙氨酸、D-色氨酸和SC-45647与Tas1r3有显著连锁,但甘氨酸、L-脯氨酸、L-丙氨酸或L-谷氨酰胺没有。对于非甜味的奎宁、柠檬酸、盐酸、氯化钠、氯化钾、味精、5'-肌苷酸或谷氨酸铵的行为或神经反应,未检测到与4号染色体远端的连锁。这些结果表明,Tas1r3基因的等位基因变异影响对某些但不是所有甜味剂的味觉神经和行为反应。本研究使用体内方法描述了T1R3受体的配体敏感性范围,据我们所知这是味觉神经活动的首次基因定位研究。