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Genetic variation in Glp1r expression influences the rate of gastric emptying in mice.

机译:Glp1r表达的遗传变异影响小鼠胃排空的速度。

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We demonstrated previously that food intake traits map to a quantitative trait locus (QTL) on proximal chromosome 17, which encompasses Glp1r (glucagon-like peptide 1 receptor), encoding an important modulator of gastric emptying. We then confirmed this QTL in a B6.CAST-17 congenic strain that consumed 27% more carbohydrate and 17% more total calories, yet similar fat calories, per body weight compared with the recipient C57BL/6J. The congenic strain also consumed greater food volume. The current aims were to 1) identify genetic linkage for total food volume in F(2) mice, 2) perform gene expression profiling in stomach of B6.CAST-17 congenic mice using oligonucleotide arrays, 3) test for allelic imbalance in Glp1r expression, 4) evaluate gastric emptying rate in parental and congenic mice, and 5) investigate a possible effect of genetic variation in Glp1r on gastric emptying. A genome scan revealed a single QTL for total food volume (Tfv1) (log of the odds ratio = 7.6), which was confirmed in B6.CAST-17 congenic mice. Glp1r exhibited allelic imbalance in stomach, which correlated with accelerated gastric emptying in parental CAST and congenic B6.CAST-17 mice. Moreover, congenic mice displayed an impaired gastric emptying response to exendin-(9-39). These results suggest that genetic variation in Glp1r contributes to the strain differences in gastric emptying rate.
机译:我们以前证明食物摄入性状映射到近端染色体17上的数量性状基因座(QTL),该基因座包含Glp1r(胰高血糖素样肽1受体),编码胃排空的重要调节剂。然后,我们在B6.CAST-17同系菌株中证实了此QTL,与接收者C57BL / 6J相比,该菌株每单位体重消耗的碳水化合物多27%,总卡路里多17%,但脂肪卡路里相似。该同系菌株也消耗了更多的食物。目前的目标是:1)确定F(2)小鼠总食物量的遗传连锁; 2)使用寡核苷酸阵列在B6的胃中进行基因表达谱分析; 3)测试Glp1r表达的等位基因失衡(4)评估亲本和同系小鼠的胃排空率,以及(5)研究Glp1r遗传变异对胃排空的可能影响。基因组扫描显示单个QTL的总食物量(Tfv1)(优势比对数= 7.6),已在B6.CAST-17同系小鼠中得到证实。 Glp1r在胃中表现出等位基因失衡,这与亲本CAST和同基因B6.CAST-17小鼠的胃排空加快有关。此外,同基因小鼠表现出对exendin-(9-39)的胃排空反应受损。这些结果表明,Glp1r的遗传变异导致了胃排空率的差异。

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