HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/R207    most recent 00491.2006v1 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 Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Kumar, K. G. Articles by Richards, B. K. S. Search for Related Content PubMed PubMed Citation Articles by Kumar, K. G. Articles by Richards, B. K. S.

APPETITE, OBESITY, DIGESTION, AND METABOLISM

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

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

Submitted 12 July 2006 ; accepted in final form 28 August 2006

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 wild-type 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 mice. 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 accommodation 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.

CAST; genetic linkage; genetics; food intake; macronutrient

This article has been cited by other articles:

				K. G. Kumar, L. O. Byerley, J. Volaufova, D. J. Drucker, G. A. Churchill, R. Li, B. York, A. Zuberi, and B. K. S. Richards Genetic variation in Glp1r expression influences the rate of gastric emptying in mice Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R362 - R371. [Abstract] [Full Text] [PDF]

				G. Cutler, L. A. Marshall, N. Chin, H. Baribault, and P. D. Kassner Significant gene content variation characterizes the genomes of inbred mouse strains Genome Res., December 1, 2007; 17(12): 1743 - 1754. [Abstract] [Full Text] [PDF]

				J. Kaput Nutrient selection through nutrigenomic approaches Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R204 - R206. [Full Text] [PDF]