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RNA Expression in the left lateral lobe of the liver in BALB/cJ and BALB/cByJ substrains of mice to identify candidate mechanisms for Oxycodone QTLs

ABSTRACT: We found BALB/cByJ and BALB/cJ mice differ in their responses to oxycodone state dependent conditioned place preference, whole brain [oxycodone] and its metabolites [noroxycodone] and [oxymorphone] following oxycodone administration, the 53.5°C hot plate, mechanical stimulation in the von Frey test, and gross brain weight. We then identified a quantitative trait locus (QTL) on chromosome 15 for whole brain [Oxymorphone] (LOD = 7.07; p < 0.001), 13 for hot plate sensitivity (LOD = 10.7; p < 0.001; peak = 56 Mb) and a QTL for brain weight on chromosome 5 (LOD = 8.7; p < 0.001). These tissues were used to investigate the transcriptome of the liver in parental strain mice in order to generate hypothosis concerning the quantitative trait mechanism for our observed effects.

ORGANISM(S): Mus musculus

PROVIDER: GSE198375 | GEO | 2022/03/14

REPOSITORIES: GEO

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RNA Expression QTL mapping in an F2 cross of BALB/cJ and BALB/cByJ mice to identify candidate genes for behavioral/metabolic QTLs

Project description:We found BALB/cByJ and BALB/cJ mice differ in their responses to oxycodone state dependent conditioned place preference, whole brain [oxycodone] and its metabolites [noroxycodone] and [oxymorphone] following oxycodone administration, the 53.5°C hot plate, mechanical stimulation in the von Frey test, and gross brain weight. We then identified a quantitative trait locus (QTL) on chromosome 15 for whole brain (LOD = 7.07; p < 0.001), 13 for hot plate sensitivity (LOD = 10.7; p < 0.001; peak = 56 Mb) and a QTL for brain weight on chromosome 5 (LOD = 8.7; p < 0.001). These tissues were used for expression QTL mapping to highlight the candidate genes Zhx2 (57 Mb) as the top transcript with the strongest association at the ch15 oxymorphone locus and identified H2afy (56 Mb) as the top transcript with the strongest association at the ch13 hot plate locus.

2022-02-11 | GSE196334 | GEO

RNA Expression QTL mapping in Striatum of an F2 cross of BALB/cJ and BALB/cByJ mice to identify candidate genes for behavioral/metabolic QTLs

2022-02-11 | GSE196352 | GEO

Genetic basis of thermal nociceptive sensitivity and brain weight in a BALB/c reduced complexity cross: BALB/cJ vs BALB/cByJ Spinal Cord RNAseq

Project description:We found BALB/cByJ mice showed enhanced sensitivity on the 53.5°C hot plate and mechanical stimulation in the von Frey test compared to BALB/cJ mice and replicated decreased gross brain weight in BALB/cByJ versus BALB/cJ. We then identified a quantitative trait locus (QTL) on chromosome 13 for hot plate sensitivity (LOD = 10.7; p < 0.001; peak = 56 Mb) and a QTL for brain weight on chromosome 5 (LOD = 8.7; p < 0.001). Expression QTL mapping of brain tissues identified H2afy (56.07 Mb) as the top transcript with the strongest association at the hot plate locus (FDR = 0.0002) and spliceome analysis identified differential exon usage within H2afy associated with the same locus. These data are spinal cord RNAseq to confirm differential expression of H2afy and other candidate genes.

2022-02-10 | GSE196302 | GEO

C57BL/6 substrain differences in inflammatory and neuropathic nociception and genetic mapping of a major quantitative trait locus underlying acute thermal nociception

Project description:Sensitivity to different pain modalities has a genetic basis that remains largely unknown. The use of closely related inbred mouse strains can facilitate gene mapping of nociceptive behaviors in preclinical pain models. We previously reported enhanced sensitivity to acute thermal nociception in C57BL/6J (B6J) versus C57BL/6N (B6N) substrains. Here, we expanded on pain phenotypes and observed an increase in inflammatory nociceptive behaviors induced by hindpaw formalin injections in B6J versus B6N mice (Charles River Laboratories). No strain differences were observed in mechanical or thermal hypersensitivity or in paw diameter following the Complete Freund s Adjuvant (CFA) model of inflammatory pain, indicating specificity in the inflammatory nociceptive stimulus. In the chronic nerve constriction injury (CCI), a model of neuropathic pain, no strain differences were observed in baseline mechanical threshold or in mechanical hypersensitivity up to one month post-CCI. We replicated the enhanced thermal nociception in B6J mice in the 52.5 C hot plate test relative to B6N mice from The Jackson Laboratory. Using a B6J x B6N-F2 cross (N=164), we mapped a major QTL underlying hot plate sensitivity to chromosome 7 that peaked at 26 Mb (LOD = 3.81, 8.74 Mb-36.50 Mb) that was more pronounced in males. Genes containing expression QTLs (eQTLs) associated with the peak nociceptive marker that have been implicated in pain and inflammation include Ryr1, Cyp2a5, Pou2f2, Clip3, Sirt2, Actn4, and Ltbp4 (FDR < 0.05). Future studies involving positional cloning and gene editing will determine the quantitative trait gene(s) and potential pleiotropy of this locus across other pain modalities. RNA-seq data and genotype information from striatum punches of F2 C57BL/6J (B6J) cross C57BL/NJ (B6NJ) oxycodone-treated mice. Genotypes are given relative to B6J allele, eg 0 = homozygous B6J.

2018-11-26 | GSE119719 | GEO

Genetic variation in Glp1r expression influences the rate of gastric emptying

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

Characterization of QTL and eQTL linked with early Fusarium graminearum infection and deoxynivalenol levels in a Wuhan -1 x Nyubai doubled-haploid wheat population at two days post inoculation

Project description:In this study, early infection by F. graminearum was characterized in a doubled-haploid population derived from the cross of the moderately FHB resistant wheat genotypes Wuhan 1 and Nyubai. Three significant QTL were identified: 1AL was associated with reduced deoxynivalenol levels, and 4BS and 5A were associated with reduced F. graminearum levels at 2 days after infection. The early resistance alleles for 1AL and 4BS were inherited from Wuhan 1, and those for the 5A QTL were inherited from Nyubai. The LOD support interval for the 5A QTL was in the same region as FHB5, a QTL previously associated with field resistance to FHB. Cis and trans eQTL were identified using RNA sequencing data from infected head samples. In total, 240 cis eQTL and 17,401 trans eQTL were identified within LOD support intervals for the three QTL. Hotspots for trans eQTL were identified within LOD support intervals for the 1AL and 4BS QTL. Differential gene expression analysis revealed twenty genes with cis eQTL within one of the 3 QTL support intervals, that had higher expression associated with FHB early resistance, and 17 genes with higher expression associated with FHB early susceptibility. Among those, genes with a cis eQTL peak coinciding with QTL peaks were enriched in functions related to signaling and protein-protein interaction, including NBS-LRR, BAH, LRR/F-box and TPR domain-containing proteins. Several genes located within one of the three QTL support intervals also had a trans eQTL with a peak at the same position as QTL peaks on other chromosomes, suggesting interactions between the QTL.

2019-11-13 | GSE123548 | GEO

QTL for renal and cardiac function during Angiotensin II and high-sodium treatment of a backcross between C57BL/6J-to-Balb/CJ-F1 and Balb/CJ

Project description:Balb/CJ mice develop heart failure and quickly decompensate during combination treatment with Angiotensin II and high-sodium diet, while C57BL/6J mice do not. Balb/CJ show a predominantly diastolic heart failure, signs of increased pulmonary pressure, relative sodium and fluid retention, peripheral edema and decompensate with anuria in a cardiorenal syndrome. A F1 cross between the strains have a similar phenotype as C57BL/6J, i.e. is protected. The present study used a second generation backcross of the F1-generation to Balb/CJ and pheotyped a wide variety of renal and circulatory and cardiac traits, identifying 9 new QTL.

2019-06-13 | E-MTAB-8047 | biostudies-arrayexpress

GEP of the murine cell line BAL17 (BALB/c)

Project description:GEP of the murine cell line BAL17 (BALB/c) BAL17- / BAL17VII-induced primary CNS lymphoma analysis. 5x10^5 cells were implanted into the brain of BALB/c wt mice and analyzed 21 and 28 days post implantation. The cell lines were also analyzed.

2013-04-10 | E-GEOD-38675 | biostudies-arrayexpress

Genetic basis of thermal nociceptive sensitivity and brain weight in a BALB/c reduced complexity cross: BALB/cJ vs BALB/cByJ Spinal Cord RNAseq

Project description:Genetic basis of thermal nociceptive sensitivity and brain weight in a BALB/c reduced complexity cross: BALB/cJ vs BALB/cByJ Spinal Cord RNAseq

| PRJNA804210 | ENA

Expression QTL mapping of chicken femoral bone

Project description:Expression quantitative trait locus (QTL) mapping of 127 adult femoral bone samples from a Red Junglefowl x White Leghorn advanced intercross line. Bone trait QTL have been mapped in the same cross, allowing a genetical genomics approach to quantitative trait gene identification

2015-10-31 | E-MTAB-3141 | biostudies-arrayexpress

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