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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)

Authors: K Ganesh, Kumar; Angela C, Poole; Barbara, York; Julia, Volaufova; Aamir, Zuberi; Brenda K Smith, Richards;

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

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.

Keywords

DNA, Complementary, Blotting, Western, Body Weight, Quantitative Trait Loci, Lactoylglutathione Lyase, Genetic Variation, DNA, Chromosomes, Mammalian, Dietary Fats, Glucagon-Like Peptide-1 Receptor, Mice, Inbred C57BL, Mice, Mice, Congenic, Phenotype, Dietary Carbohydrates, Animals, RNA, Dietary Proteins, Energy Intake, Microsatellite Repeats

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Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
31
Average
Top 10%
Top 10%