期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 294, 期 2, 页码 R362-R371出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00640.2007
关键词
quantitative trait locus; glucagon-like peptide 1 receptor
类别
资金
- NIDDK NIH HHS [1P30 DK 072476, P30 DK072476, DK 53113, R01 DK053113] Funding Source: Medline
- NIGMS NIH HHS [GM 070683] Funding Source: Medline
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.
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