Bachmanov Alexander A, Reed Danielle R, Li Xia, Beauchamp Gary K
Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA.
Pure Appl Chem. 2002 Jul 1;74(7):1135-1140. doi: 10.1351/pac200274071135.
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.
近交系小鼠品系对甜味溶液的喜好程度存在显著差异，部分原因是品系间的基因差异。我们运用多种技术，在整个基因组中定位了多个影响甜味剂接受度的区域。调节小鼠品系间甜味剂偏好差异的一个重要位点是位于4号染色体远端的糖精偏好（Sac）位点。味觉神经对甜味剂的传入反应也因Sac位点的等位基因差异而有所不同，这表明该基因可能编码一种甜味受体。通过位置克隆方法，我们鉴定出一个基因（Tas1r3），它编码假定味觉受体T1R家族的第三个成员T1R3。将含有来自高甜味剂偏好品系的Tas1r3等位基因的染色体片段通过连续回交导入低甜味剂偏好品系的遗传背景中，挽救了其低甜味剂偏好表型。Tas1r3有两种常见的单倍型，一种存在于甜味剂偏好较高的小鼠品系中，另一种存在于对甜味剂相对不敏感的品系中。这项研究与其他实验室近期的补充研究共同提供了有力证据，证明Tas1r3等同于Sac位点，并且T1R3受体（与味觉受体T1R2共表达时）对甜味剂有反应。然而，可能还有其他甜味受体有待发现。
