Monell Chemical Senses Center, Philadelphia, PA, USA.
Laboratory of Cellular Neurobiology, School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo, Japan.
Mamm Genome. 2021 Apr;32(2):51-69. doi: 10.1007/s00335-021-09858-4. Epub 2021 Mar 13.
Mice of the C57BL/6ByJ (B6) strain have higher consumption of sucrose, and stronger peripheral neural responses to it, than do mice of the 129P3/J (129) strain. To identify quantitative trait loci (QTLs) responsible for this strain difference and to evaluate the contribution of peripheral taste responsiveness to individual differences in sucrose intake, we produced an intercross (F) of 627 mice, measured their sucrose consumption in two-bottle choice tests, recorded the electrophysiological activity of the chorda tympani nerve elicited by sucrose in a subset of F mice, and genotyped the mice with DNA markers distributed in every mouse chromosome. We confirmed a sucrose consumption QTL (Scon2, or Sac) on mouse chromosome (Chr) 4, harboring the Tas1r3 gene, which encodes the sweet taste receptor subunit TAS1R3 and affects both behavioral and neural responses to sucrose. For sucrose consumption, we also detected five new main-effect QTLs, Scon6 (Chr2), Scon7 (Chr5), Scon8 (Chr8), Scon3 (Chr9), and Scon9 (Chr15), and an epistatically interacting QTL pair Scon4 (Chr1) and Scon3 (Chr9). No additional QTLs for the taste nerve responses to sucrose were detected besides Scon2 (Tas1r3) on Chr4. Identification of the causal genes and variants for these sucrose consumption QTLs may point to novel mechanisms beyond peripheral taste sensitivity that could be harnessed to control obesity and diabetes.
C57BL/6ByJ（B6）品系的小鼠比 129P3/J（129）品系的小鼠消耗更多的蔗糖，对其外周神经反应也更强。为了确定导致这种品系差异的数量性状基因座（QTL），并评估外周味觉反应对蔗糖摄入量个体差异的贡献，我们产生了一个 627 只小鼠的杂交（F1）群体，在双瓶选择试验中测量它们的蔗糖消耗量，在 F1 小鼠的亚群中记录由蔗糖引起的鼓索神经的电生理活性，并使用分布在每只小鼠染色体上的 DNA 标记对小鼠进行基因分型。我们证实了一个位于第 4 号染色体（Chr4）上的蔗糖消耗 QTL（Scon2，或 Sac），该 QTL 包含 Tas1r3 基因，该基因编码甜味受体亚基 TAS1R3，影响对蔗糖的行为和神经反应。对于蔗糖消耗，我们还检测到五个新的主效 QTL，Scon6（Chr2）、Scon7（Chr5）、Scon8（Chr8）、Scon3（Chr9）和 Scon9（Chr15），以及一个上位相互作用的 QTL 对 Scon4（Chr1）和 Scon3（Chr9）。除了第 4 号染色体上的 Scon2（Tas1r3）之外，没有检测到与蔗糖对味觉神经反应相关的其他 QTL。这些蔗糖消耗 QTL 的因果基因和变体的鉴定可能会揭示出除外周味觉敏感性之外的新机制，这些机制可以被利用来控制肥胖和糖尿病。
