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Genetic controls of Tas1r3 -independent sucrose consumption in mice
Mammalian Genome ( IF 2.7 ) Pub Date : 2021-03-12 , DOI: 10.1007/s00335-021-09860-w
Cailu Lin 1 , Michael G Tordoff 1 , Xia Li 1, 2 , Natalia P Bosak 1 , Masashi Inoue 1, 3 , Yutaka Ishiwatari 1, 4 , Longhui Chen 1, 5 , Gary K Beauchamp 1 , Alexander A Bachmanov 1, 6 , Danielle R Reed 1
Affiliation  

We have previously used crosses between C57BL/6ByJ (B6) and 129P3/J (129) inbred strains to map a quantitative trait locus (QTL) on mouse chromosome (Chr) 4 that affects behavioral and neural responses to sucrose. We have named it the sucrose consumption QTL 2 (Scon2), and shown that it corresponds to the Tas1r3 gene, which encodes a sweet taste receptor subunit TAS1R3. To discover other sucrose consumption QTLs, we have intercrossed B6 inbred and 129.B6-Tas1r3 congenic mice to produce F2 hybrids, in which Scon2 (Tas1r3) does not segregate, and hence does not contribute to phenotypical variation. Chromosome mapping using this F2 intercross identified two main-effect QTLs, Scon3 (Chr9) and Scon10 (Chr14), and an epistatically interacting QTL pair Scon3 (Chr9)–Scon4 (Chr1). Using serial backcrosses, congenic and consomic strains, we conducted high-resolution mapping of Scon3 and Scon4 and analyzed their epistatic interactions. We used mice with different Scon3 or Scon4 genotypes to understand whether these two QTLs influence sucrose intake via gustatory or postoral mechanisms. These studies found no evidence for involvement of the taste mechanisms, but suggested involvement of energy metabolism. Mice with the B6 Scon4 genotype drank less sucrose in two-bottle tests, and also had a higher respiratory exchange ratio and lower energy expenditure under basal conditions (when they had only chow and water available). Our results provide evidence that Scon3 and Scon4 influence mouse-to-mouse variation in sucrose intake and that both likely act through a common postoral mechanism.



中文翻译:

小鼠中 Tas1r3 非依赖性蔗糖消耗的遗传控制

我们以前使用 C57BL/6ByJ (B6) 和 129P3/J (129) 近交系之间的杂交来绘制小鼠染色体 (Chr) 4 上影响对蔗糖的行为和神经反应的数量性状基因座 (QTL)。我们将它命名为蔗糖消费QTL 2(Scon2),并表明它对应于Tas1r3基因其编码甜味受体亚单位TAS1R3。为了发现其他消耗蔗糖的 QTL,我们将 B6 近交系和 129.B6- Tas1r3同类系小鼠杂交以产生 F 2杂种,其中Scon2 ( Tas1r3 ) 不分离,因此对表型变异没有贡献。使用此 F 2 的染色体作图intercross确定了两个主效应 QTL,Scon3 (Chr9) 和Scon10 (Chr14),以及一个上位相互作用的 QTL 对Scon3 (Chr9) –Scon4 (Chr1)。使用串行回交,同类和consomic株,我们进行的高分辨率测绘Scon3Scon4并分析其上位相互作用。我们使用具有不同Scon3Scon4基因型的小鼠来了解这两个 QTL 是否通过味觉或口腔机制影响蔗糖摄入。这些研究没有发现味觉机制参与的证据,但暗示了能量代谢的参与。带有 B6 Scon4 的小鼠基因型在两瓶测试中饮用较少的蔗糖,并且在基础条件下(当它们只有食物和水可用时)具有较高的呼吸交换率和较低的能量消耗。我们的研究结果提供了证据,表明Scon3Scon4 会影响小鼠间蔗糖摄入量的变化,并且两者都可能通过共同的口服机制起作用。

更新日期:2021-03-12
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