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Am J Physiol Regul Integr Comp Physiol (August 31, 2006). doi:10.1152/ajpregu.00491.2006
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Submitted on July 12, 2006
Accepted on August 28, 2006

Quantitative trait loci for carbohydrate and total energy intake on mouse Chromosome 17: Congenic strain confirmation and candidate gene analyses (Glo1, Glp1r)

K. Ganesh Kumar1, Angela C. Poole1, Barbara York1, Julia Volaufova2, Aamir Zuberi3, and Brenda K. Smith Richards1*

1 Experimental Obesity Division, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
2 Biostatistics Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States
3 Division of Nutrition and Chronic Diseases,, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States

* To whom correspondence should be addressed. E-mail: richarbk{at}pbrc.edu.

Quantitative trait loci (QTL) for carbohydrate (Mnic1) and total energy (Kcal2) intake on proximal mouse Chromosome 17 were identified previously from a C57BL/6J (B6) X CAST/Ei (CAST) intercross. Here we report that a new congenic strain developed in our laboratory has confirmed this complex locus by recapitulating the original linked phenotypes: B6.CAST-17 homozygous congenic mice consumed more carbohydrate (27%) and total energy (17%) compared with littermate wildtype mice. Positional gene candidates with relevance to carbohydrate metabolism, glyoxalase I (Glo1) and glucagon-like peptide 1 receptor (Glp1r), were evaluated. Glo1 expression was upregulated in liver and hypothalamus of congenic mice when compared with B6. Analyses of Glp1r mRNA and protein expression revealed tissue-specific strain differences in pancreas (congenic>B6) and stomach (B6>congenic). These results suggest the possibility of separate mechanisms for enhanced insulin synthesis and gastric accomodation in the presence of high carbohydrate intake and larger food volume, respectively. Sequence analysis of Glp1r found a G insert at nt position 1349 which results in earlier termination of the open reading frame, thus revealing an error in the public sequence. Consequently, the predicted length of GLP-1R is 463 aa compared with 489 aa as previously reported. Also we found a polymorphism in Glp1r between parental strains that alters the amino acid sequence. Variation in Glp1r could influence nutrient intake in this model through changes in the regulatory or protein coding regions of the gene. These congenic mice offer a powerful tool for investigating gene interactions in the control of food intake.




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