CAST x C57 QTLs Effect on Gene Expression for Chromosomes 2, 11, and 17
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE22042 | GEO | 2010/07/30
SECONDARY ACCESSION(S): PRJNA128995
REPOSITORIES: GEO
Similar Datasets
Project description:Three congenic mouse strains were profiled with microarrays and were analyzed using a QTL/Microarray approach to identify candidate genes that regulate biometric phenotypes: HG2D (HG.CAST-(D2Mit329-D2Mit457)), HG11 (HG.CAST-(D11Mit260-D11Mit255, MGI reference: 3771218), and HG17 (HG.CAST-(D17Mit196-D17Mit190); MGI reference: 3771215). All these congenic strains isolate CAST/EiJ (CAST) alleles in a C57BL/6Jhg/hg (C57) background and bare the hg deletion in the high growth locus on chromosome 10. F2 animals from intercrossing congenic males and C57 control females were profiled for gene expresion on brain, liver and gonadal white fat. To detect differential expression produced by allelic effects of biometric QTLs on chromosomes 2, 11, and 17. Three strains were profiled: HG2D, HG11, and HG17, isolating CAST alleles in a high growth (HG) background on chromosomes 2, 11, and 17 respectively. Four biological replicates were assayed per strain for brain, liver and gonadal white adipose tissue. Experiments for each chromosomes were done independently. Only genotype comparisons within tissue in each strain were performed.
2010-07-30 | E-GEOD-22042 | biostudies-arrayexpress
Project description:Expression profiling comparing healthy kidneys of wild-type FVB mice and wild-type full congenic FVB-HIVAN1CAST mice HIV-1 transgenic mice on the FVB/NJ background (TgFVB) represent a validated model of HIV-associated nephropathy (HIVAN). A major susceptibility locus, HIVAN1, was previously mapped to chromosome 3A1-A3 in a cross between TgFVB and CAST/EiJ (CAST) strains, and introgression of a 51.9 Mb segment encompassing HIVAN1 from CAST into TgFVB results in accelerated development of nephropathy. We performed genome-wide expression profiling of whole kidneys from wild-type (without the HIV-1 transgene) full congenic FVB-HIVAN1CAST and FVB mouse strains, with the goal of identifying genes with differential renal expression in the HIVAN1 locus that may be associated with the development of nephropathy upon exposure to HIV-1. We only profiled healthy wild-type kidneys because the profound histopathological lesions of HIV-1 transgenic mice introduce many secondary gene expression changes that can confound interpretation of transcriptomic data.
2016-09-01 | GSE86269 | GEO
Project description:The specific genes influencing the quantitative variation in macronutrient preference and food intake are virtually unknown. We refined a previously identified mouse chromosome 17 (MMU17) region harboring quantitative trait loci (QTL) with large effects on preferential macronutrient intake-carbohydrate (Mnic1), total kilcalories (Kcal2), and total food volume (Tfv1) using interval-specific congenic strains. These loci were isolated in the [C57BL/6J.CAST/EiJ-17.1-(D17Mit19-D17Mit50); B6.CAST-17.1] strain, developed by introgressing a ~40.1 Mb CAST MMU17 region into recipient B6 genome. In a diet selection paradigm (carbohydrate/protein vs. fat/protein), these B6.CAST-17.1 sub-congenic mice eat 30% more calories from the carbohydrate-rich diet, ~10% more total calories, and ~9% more total food volume per body weight. In the current study, this carbohydrate-preferring B6.CAST-17.1 subcongenic strain was crossed with the fat-preferring inbred B6 strain to generate a subcongenic-derived F2 mapping population; genotypes were determined using a high-density, custom SNP panel. The main outcome of this study is that genetic linkage analysis greatly reduced the 95% confidence interval (CI) for Mnic1 (encompassing Kcal2 and Tfv1) from 40.1 to 29.5 Mb and more precisely established the QTL boundaries. Specifically, the genetic architecture for Mnic1 (preferential carbohydrate intake) does not follow the same pattern as that for co-localized Kcal2/Tfv1 (total kcal and food volume, respectively), suggesting the presence of separate quantitative trait genes for these food intake traits. No genetic linkage for self-selected fat intake was detected, underscoring the carbohydrate-specific effects of this MMU17 locus. The Mnic1/Kcal2/Tfv1 QTL was further de-limited to a ~19.1 Mb interval, based on the absence of macronutrient diet selection phenotypes in subcongenic HQ17IIa mice that possess CAST MMU17 donor segment on a C57BL/6Jhg/hg background. A second key finding is the separation of two energy balance QTLs: Mnic1/Kcal2/Tfv1 for food intake and a newly discovered locus regulating short term body weight gain. The genes Decr2, Ppard and Agapt1 in the critical QTL interval were identified and prioritized using a combination of genome sequence analysis, and tag-based transcriptome sequencing to measure hypothalamic gene expression in non-recombinant F2 controls, possessing cast/cast and b6/b6 genotypes across the sub-congenic segment.
2015-05-15 | GSE60756 | GEO
Project description:A C57BL6/J (B6) x CAST/Ei (CAST) strain intercross was used to identify the first mammalian QTL for macronutrient-specific intake (carbohydrate and fat) and for total energy intake. A region on proximal Chromosome 17 revealed two significant QTL that co-localized for increased macronutrient intake-carbohydrate (Mnic1) and total kilocalorie intake (Kcal2), adjusted for body weight. An interval-specific congenic strain, B6.CAST-17, was then developed which verified the QTL. A new sub-congenic strain was developed which retained the linked traits. Important new findings emerged shows that this congenic interval confers an activity phenotype, i.e., mice carrying the differential segment have 20% higher spontaneous physical activity levels compared with the host B6 strain. We hypothesize that this Chromosome 17 QTL is either encoded by a single gene locus that determines both food intake and physical activity, or by two or more genes, each determining a sub-phenotype of energy balance. Microarray analysis of skeletal muscle and hypothalamus in congenic and wild type B6 mice was carried out to identify potential candidate genes for the activity and food intake behavior. Keywords: macronutrient-specific intake, sub-congenic strain
2009-02-12 | GSE10517 | GEO
Project description:A C57BL6/J (B6) x CAST/Ei (CAST) strain intercross has revealed a new quantitative trait locus (QTL) on Chromosome (Chr) 17 controlling total food volume (Tfv1; LOD=7.6). Compared with B6, the CAST mice consume 39% more food volume per body weight in a macronutrient diet selection paradigm. Linkage analyses of total food volume revealed the presence of suggestive QTL on Chrs 2, 6, and 15 and a significant locus on Chr 17. An interval-specific congenic strain, B6.CAST-17, was then developed which verified the QTL. Microarray analysis of stomach in congenic and wildtype B6 mice revealed Glp1r as an expression candidate with physiological relevance to food intake. Further functional analysis of this gene revealed this gene as potential candidate for total food volume trait in mice Keywords: Comparative gene expression analysis
2008-02-13 | GSE7756 | GEO
Project description:The specific genes influencing the quantitative variation in macronutrient preference and food intake are virtually unknown. We refined a previously identified mouse chromosome 17 (MMU17) region harboring quantitative trait loci (QTL) with large effects on preferential macronutrient intake-carbohydrate (Mnic1), total kilcalories (Kcal2), and total food volume (Tfv1) using interval-specific congenic strains. These loci were isolated in the [C57BL/6J.CAST/EiJ-17.1-(D17Mit19-D17Mit50); B6.CAST-17.1] strain, developed by introgressing a ~40.1 Mb CAST MMU17 region into recipient B6 genome. In a diet selection paradigm (carbohydrate/protein vs. fat/protein), these B6.CAST-17.1 sub-congenic mice eat 30% more calories from the carbohydrate-rich diet, ~10% more total calories, and ~9% more total food volume per body weight. In the current study, this carbohydrate-preferring B6.CAST-17.1 subcongenic strain was crossed with the fat-preferring inbred B6 strain to generate a subcongenic-derived F2 mapping population; genotypes were determined using a high-density, custom SNP panel. The main outcome of this study is that genetic linkage analysis greatly reduced the 95% confidence interval (CI) for Mnic1 (encompassing Kcal2 and Tfv1) from 40.1 to 29.5 Mb and more precisely established the QTL boundaries. Specifically, the genetic architecture for Mnic1 (preferential carbohydrate intake) does not follow the same pattern as that for co-localized Kcal2/Tfv1 (total kcal and food volume, respectively), suggesting the presence of separate quantitative trait genes for these food intake traits. No genetic linkage for self-selected fat intake was detected, underscoring the carbohydrate-specific effects of this MMU17 locus. The Mnic1/Kcal2/Tfv1 QTL was further de-limited to a ~19.1 Mb interval, based on the absence of macronutrient diet selection phenotypes in subcongenic HQ17IIa mice that possess CAST MMU17 donor segment on a C57BL/6Jhg/hg background. A second key finding is the separation of two energy balance QTLs: Mnic1/Kcal2/Tfv1 for food intake and a newly discovered locus regulating short term body weight gain. The genes Decr2, Ppard and Agapt1 in the critical QTL interval were identified and prioritized using a combination of genome sequence analysis, and tag-based transcriptome sequencing to measure hypothalamic gene expression in non-recombinant F2 controls, possessing cast/cast and b6/b6 genotypes across the sub-congenic segment. Global gene expression profiles in the hypothalamus were compared between non-recombinant subcongenic-derived F2 mice, possessing a genotype of cast/cast (n=12) or b6/b6 (n=12) across the Chr 17 subcongenic segment and b6/b6 across the rest of the genome. RNA was isolated from individual mice of each genotype that were selected for study. Specifically, twelve mice of each genotype that displayed the most divergent phenotypic values for self-selected carbohydrate and total kcal intake were chosen for gene expression analysis, i.e., cast/cast mice with the highest and b6/b6 mice with the lowest kcal intake from carbohydrate, or the 25% tails of the distribution. Tissues were harvested ~48 h after re-initiation of the carbohydrate/protein vs. fat/protein diets, following an extended wash-out period on chow diet after completion of the 10 d macronutrient selection test.
2015-05-15 | E-GEOD-60756 | biostudies-arrayexpress
Project description:TAZ knockout (KO/Y) and littermate control (WT/Y) mice were generated by crossing TAZ(KO/X) females in the C57BL6J background to male mice from C57BL6J, CAST/EiJ or A/J backgrounds. F1 mutant males in C57 and CAST-F1 backgrounds had cardiomyopathy and low heart function, whereas A/J F1 mutant males had normal heart function.
2023-12-05 | GSE221675 | GEO
Project description:The goal of this experiment was to identify genes contributing to fat, carbohydrate, and total calorie intake in mice by comparing gene expression in liver and hypothalamus of an interval-specific congenic strain, B6.CAST-17, with that of the control strain. This congenic strain has previously confirmed genetic loci on Chr 17 linked to increased carbohydrate (Mnic1) and kilocalorie (Kcal2) intake. Keywords: Comparative gene expression analysis
2007-12-11 | GSE6507 | GEO
Project description:The phosphorylation state of human HA-tagged-SIK2, adenovirally introduced in murine hepatocytes (C57/BL/6 strain) was analysed in unstimulated and in response to glucagon- or insulin- treated conditions. Background:- LKB1 is a master kinase that regulates metabolism and growth through AMPK and 12 other closely-related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. The salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressor downstream of LKB1 in the liver. A selective SIK inhibitor (HG-9-91-01) promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive-mutant-SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation/activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver.
2014-08-08 | PXD001032 | Pride