Submitted on September 5, 2007
Accepted on December 7, 2007
Genetic variation in Glp1r expression influences the rate of gastric emptying in mice
K. Ganesh Kumar1, Lauri Byerley2, Julia Volaufova3, Daniel J. Drucker4, Gary A. Churchill5, Renhua Li5, Barbara York6, Aamir Zuberi7, and Brenda K. Smith Richards1*
1 Experimental Obesity, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
2 Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
3 Biostatistics Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States
4 The Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Canada
5 The Jackson Laboratory, Bar Harbor, Maine, United States
6 Baton Rouge, Louisiana, United States; Experimental Obesity, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
7 Division of Experimental Obesity, Division of Nutrition and Chronic Diseases, Pennington Biomedical Research Center, United States
* To whom correspondence should be addressed. E-mail: richarbk{at}pbrc.edu.
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 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) (LOD=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/Ei 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.
