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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/R362    most recent 00640.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kumar, K. G. Articles by Richards, B. K. S. PubMed PubMed Citation Articles by Kumar, K. G. Articles by Richards, B. K. S.

APPETITE, OBESITY, DIGESTION, AND METABOLISM

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

¹Divisions of Experimental Obesity, and ²Nutrition and Chronic Diseases, ³Stable Isotope Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge; ⁴Biostatistics Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana; ⁵The Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; and ⁶The Jackson Laboratory, Bar Harbor, Maine

Submitted 5 September 2007 ; accepted in final form 7 December 2007

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 F₂ 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.

quantitative trait locus; glucagon-like peptide 1 receptor