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. Overall design: C57BL/6J (B6J) and C57BL/NJ (B6NJ) mice were purchased from JAX at 7 weeks of age and were habituated in the vivarium one week prior to experimental testing that occurred next door. B6J females were crossed to B6NJ males to generate B6J x B6NJ-F1 mice and B6J x B6NJ F1 offspring were intercrossed to generate B6J x B6NJ F2 mice. Mice were 50-100 days old at the time of testing. F2 mice recieved four daily oxycodone injections (20 mg/kg, i.p.). Ninety SNP markers spaced approximately 30 Mb (approximately 15 cM) apart were genotyped using a custom-designed Fluidigm array.
C57BL/6 substrain differences in inflammatory and neuropathic nociception and genetic mapping of a major quantitative trait locus underlying acute thermal nociception.
Sex, Age, Subject
View SamplesCellular mechanisms that contribute to low estradiol concentrations produced by the preovulatory ovarian follicle in cattle with a compromised metabolic status (such as lactatino) are largely unknown. To gain insight into the main metabolic mechanisms affecting preovulatory follicle function RNAseq profiling was conducted on non-lactating Holstein-Friesian heifers (n=16) and lactating Holstein-Friesian cows (n=17) at three stages of preovulatory follicle development: A) newly selected dominant follicle in the luteal phase (Selection); B) follicular phase before the LH surge (Differentiation) and C) pre-ovulatory phase after the LH surge (Luteinization). Based on a combination of RNA sequencing, ingenuity pathway analysis and Q-RT-PCR validation several important molecular markers involved in steroid biosynthesis, such as the expression of steroidogenic acute regulatory protein (STAR) within developing dominant follicles, were identified to be affected (downregulated) by the catabolic state. We propose that the adverse metabolic environment caused by lactation decreases preovulatory follicle function by affecting cholesterol transport into the mitochondria to initiate steroidogenesis. Overall design: Granulosa and Theca samples from the dominant follicle were taken from cows and heifers at stages: selection, differentiation and luteinization.
Effect of the metabolic environment at key stages of follicle development in cattle: focus on steroid biosynthesis.
Specimen part, Subject
View SamplesRNA-seq analysis of 16 B6J x B6NJ-F2 mice which are homozygous for either the wild-type B6J allele (binge-resistant; J/J) or mutant B6NJ allele (binge-prone; N/N), at rs240617401, a marker denoting a missense SNP in Cyfip2. Genotype identity is denoted as either J for binge-resistant; J/J, or N for binge-prone; N/N. Overall design: A sample size of N=8 per genotype was employed (4 females, 4 males; 69-100 days old at the time of sacrifice). Striatum punches were harvested on Day 24 immediately following the 5-min behavioral test on the EPM, stored in RNAlater for 48 h, blotted dry with a kimwipe, and transferred to -80ºC. Total RNA was isolated and shipped to the University of Chicago Genomics Core Facility for cDNA library preparation using the Illumina TruSeq Stranded mRNA LT Sample Prep Kit (50 bp single-end reads). Samples were sequenced using the Illumina HiSeq 4000 with 16 samples per lane over four lanes (technical quadruplicates). FASTQ files were quality checked via FASTQC and all samples exhibited Phred quality scores greater than 30 (i.e. less than 0.1% sequencing error). FASTQ files were used to align reads to the reference genome using TopHat (mm10; UCSC Genome Browser). Read counts per gene were quantified using the HTSeq Python package.
Cytoplasmic FMR1-Interacting Protein 2 Is a Major Genetic Factor Underlying Binge Eating.
Sex, Specimen part, Subject
View SamplesRNA-seq analysis of 8 Cyfip2N/- and 8 Cyfip2N/N mice. Cyfip2N/- are mice contain one copy of the B6NJ missense mutation and one copy of the nonsense mutation (binge-resistant; N/-), whereas Cyfip2N/N are mice that have two mutated B6NJ allele (binge-prone; N/N), at rs240617401, a marker denoting a missense SNP in Cyfip2. Genotype identity is denoted as either J for binge-resistant; N/-, or N for binge-prone; N/N. Overall design: A sample size of N=8 per genotype was employed (4 females, 4 males; 82-84 days old at the time of sacrifice). Striatum punches were harvested on Day 24 immediately following the 5-min behavioral test on the EPM, stored in RNAlater for 48 h, blotted dry with a kimwipe, and transferred to -80ºC. Total RNA was isolated and shipped to the University of Chicago Genomics Core Facility for cDNA library preparation using the Illumina TruSeq Stranded mRNA LT Sample Prep Kit (50 bp single-end reads). Samples were sequenced using the Illumina HiSeq 4000 with 16 samples per lane over four lanes (technical quadruplicates). FASTQ files were quality checked via FASTQC and all samples exhibited Phred quality scores greater than 30 (i.e. less than 0.1% sequencing error). FASTQ files were used to align reads to the reference genome using TopHat (mm10; UCSC Genome Browser). Read counts per gene were quantified using the HTSeq Python package.
Cytoplasmic FMR1-Interacting Protein 2 Is a Major Genetic Factor Underlying Binge Eating.
Sex, Specimen part, Cell line, Subject
View SamplesAndrogens are essential for sexual development and reproduction. However, androgen regulation in health and disease is poorly understood. Previously, we showed that human adrenocortical H295R cells grown under starvation conditions acquire a hyperandrogenic steroid profile with changes in steroid metabolizing enzymes HSD3B2 and CYP17A1 essential for androgen production. Furthermore, we have shown that metformin inhibits androgen production of steroidogenic H295R cells and inhibits complex I activity of the respriatory chain. Therefore, to search for underlying mechanisms regulting androgen production and to understand the basic biology of androgens, we have characterized the gene expression profile of H295R cells grown under normal growth conditions, serum starvation (hyperandrogenic) growth conditions as well as after metformin treatment (hypoandrogenic).
Retinoic acid receptor beta and angiopoietin-like protein 1 are involved in the regulation of human androgen biosynthesis.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.
Specimen part, Subject, Time
View SamplesThe analytical validation of a 15 gene prognostic signature for early-stage, completely resected, non-small-cell lung carcinoma that distinguishes between patients with good and poor prognoses.
Analytical Performance of a 15-Gene Prognostic Assay for Early-Stage Non-Small-Cell Lung Carcinoma Using RNA-Stabilized Tissue.
Specimen part, Subject
View SamplesSystems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans.
Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.
Specimen part, Subject, Time
View SamplesSystems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans.
Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.
Specimen part, Subject, Time
View SamplesSystems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans.
Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.
Specimen part, Subject, Time
View Samples