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Quantitative trait loci for carbohydrate and total energy intake on mouse chromosome 17: congenic strain confirmation and candidate gene analyses (Glo1, Glp1r).
- Source :
-
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2007 Jan; Vol. 292 (1), pp. R207-16. Date of Electronic Publication: 2006 Aug 31. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Animals
Blotting, Western
Body Weight physiology
DNA genetics
DNA, Complementary biosynthesis
DNA, Complementary genetics
Dietary Carbohydrates
Dietary Fats
Dietary Proteins
Genetic Variation
Glucagon-Like Peptide-1 Receptor
Mice
Mice, Congenic
Mice, Inbred C57BL
Microsatellite Repeats genetics
Phenotype
RNA genetics
RNA isolation & purification
Reverse Transcriptase Polymerase Chain Reaction
Chromosomes, Mammalian genetics
Energy Intake genetics
Lactoylglutathione Lyase genetics
Quantitative Trait Loci
Receptors, Glucagon genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6119
- Volume :
- 292
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Regulatory, integrative and comparative physiology
- Publication Type :
- Academic Journal
- Accession number :
- 16946080
- Full Text :
- https://doi.org/10.1152/ajpregu.00491.2006