Genetic variation in Glp1r expression influences the rate of gastric emptying in mice.
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.
Kumar
K Ganesh
KG
Division of Experimental Obesity, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808-4124, USA.
Byerley
Lauri O
LO
Volaufova
Julia
J
Drucker
Daniel J
DJ
Churchill
Gary A
GA
Li
Renhua
R
York
Barbara
B
Zuberi
Aamir
A
Richards
Brenda K Smith
BK
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004435:Eating / Q000235:genetics; D005746:Gastric Emptying / Q000187:drug effects / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D014644:Genetic Variation; D023281:Genomics; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018027:Receptors, Glucagon / Q000235:genetics* / Q000378:metabolism
D010446:Peptide Fragments; D018027:Receptors, Glucagon; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1