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.

中文翻译：

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甜味偏好的遗传学

近交小鼠品系在对甜溶液的亲和力方面表现出显着差异，部分原因是品系之间的遗传差异。使用多种技术，我们在整个基因组中定位了影响甜味剂接受度的多个区域。调节小鼠品系中甜味剂偏好差异的一个显着基因是糖精偏好（囊) 4 号染色体末端的基因座。味觉神经对甜味剂的传入反应也随着 Sac 基因座的等位基因差异而变化，这表明该基因可能编码一种甜味受体。使用定位克隆方法，我们鉴定了一个基因（Tas1r3) 编码推定的味觉受体 T1R 家族的第三个成员，T1R3。通过连续回交含有Tas1r3从高甜味剂偏好菌株到低甜味剂偏好菌株的遗传背景的等位基因挽救了其低甜味剂偏好表型。Tas1r3有两种常见的单倍型，一种存在于对甜味剂偏好升高的小鼠品系中，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最近的补充研究相结合，提供了令人信服的证据，表明Tas1r3相当于 Sac 基因座，并且 T1R3 受体（当与味觉受体 T1R2 共表达时）对甜味剂有反应。然而，其他甜味受体可能仍有待确定。