Project description:We hypothesize that gene expression in the aging lungs of these two strains of mice are divergent thus contributing to the disparity in the phenotypes. More specifically, (1) Aging DBA/2J mice compared to aging C57BL/6 mice are known to be accelerated in their lung physiology and morphometry; (2) C57BL/6J are known to have longer natural longevity than DBA/2J mice. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between aging lungs of both strains of mice. Keywords: comparative expression profiling
Project description:Genetic variation is known to influence the amount of mRNA produced by a gene, but the effects in different tissues is unclear. We studied gene expression levels in whole brain, kidney or liver, comparing 8 week old, male C57BL/6J to DBA/2J mice. Genes differentially expressed due to genetic background in one tissue were not differentially expressed in other tissues, suggesting that genetic variation of gene expression is tissue specific in inbred mice. Data used in a comparison to the BXD panel of mice in GSE8355, GSE8356, GSE6621 and to SJL/J in GSE8358.
Project description:We hypothesize that gene expression in the aging lungs of these two strains of mice are divergent thus contributing to the disparity in the phenotypes.re specifically, (1) Aging DBA/2J mice compared to aging C57BL/6 mice are known to be accelerated in their lung physiology andrphometry; (2) C57BL/6J are known to have longer natural longevity than DBA/2J mice. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between aging lungs of both strains of mice. Experiment Overall Design: This study utilizes microarray analysis to test these hypotheses. Three sets of lungs were harvested from both strains at each time point (C57BL/6J: 2, 18, AND 26s; DBA/2J: 2 and 18s). RNA was isolated and used for global gene expression profiling (Affymetrixuse 430 2.0 array). Statistically significant gene expression was determined as a minimum 6 counts of 9 pairwise comparisons, minimum 1.5-fold change, and p < 0.05. Further, Absolute | FC - FC SEM | >= 1.5.
Project description:C57BL/6J (B6) and DBA/2J (D2) mice were fed a high-fat/high-cholesterol diet in order to investigate the responses to that diet over time and their underlying genetic factors. We observed distinctly diverse responses between B6 and D2 mice, including dynamic distribution of cholesterol in serum and bile, hepatic apoptosis and dynamic formation of gallstones and atherosclerosis. Hepatic microarray analysis revealed distinctly different gene expression patterns in functional pathway groups including lipid metabolism, oxidative stress, immune/inflammation response and apoptosis, which might account for the different responses.This might provide us not only new insights into gallstones formation and atherosclerosis, but also opportunities to identify candidate genes for high-fat/high-cholesterol related diseases. C57BL/6J (B6) and DBA/2J (D2) mice were fed a high-fat/high-cholesterol diet in 0,1,4 12,21 weeks,respectively. Liver tissues of mice from each time-point were removed for RNA extraction. Equal amounts of RNA samples from five mice of each strain at each time-point were pooled and then used to generate biotinylated cRNA targets for Affymetrix GeneChip Mouse Genome 430 2.0 Array.
Project description:C57BL/6J (B6) and DBA/2J (D2) mice were fed a high-fat/high-cholesterol diet in order to investigate the responses to that diet over time and their underlying genetic factors. We observed distinctly diverse responses between B6 and D2 mice, including dynamic distribution of cholesterol in serum and bile, hepatic apoptosis and dynamic formation of gallstones and atherosclerosis. Hepatic microarray analysis revealed distinctly different gene expression patterns in functional pathway groups including lipid metabolism, oxidative stress, immune/inflammation response and apoptosis, which might account for the different responses.This might provide us not only new insights into gallstones formation and atherosclerosis, but also opportunities to identify candidate genes for high-fat/high-cholesterol related diseases.
Project description:Expression profiling of a cohort of mice was derived from a standard F2 intercross using two standard inbred strains, C57BL/6J and DBA/2J. In this study, we selected 127 male animals that had been raised on a standard rodent chow diet (Purina Chow from Ralston-Purina Co., St. Louis, MO) for eight weeks and then switched to a high fat diet for sixteen additional weeks. At 20 weeks of age, the mice were euthanized and liver tissues were collected and flash frozen in liquid nitrogen and stored at -80 degrees C prior to RNA isolation. All procedures of housing and treatment of animals were performed in accordance with IACUC regulations.
Project description:Retinal ganglion cell (RGC) death is the final consequence of many blinding diseases, where there is considerable variation in the time course and severity of RGC loss. Indeed, this process appears to be influenced by a wide variety of genetic and environmental factors. In this study we explored the genetic basis for differences in ganglion cell death in two inbred strains of mice. We found that RGCs are more susceptible to death following optic nerve crush in C57BL/6J mice (54% survival) than in DBA2/J mice (62% survival). Using the Illumina Mouse-6 microarray, we identified 1,580 genes with significant change in expression following optic nerve crush in these two strains of mice. Our analysis of the changes occurring after optic nerve crush demonstrated that the greatest amount of change (44% of the variance) was due to the injury itself. This included changes associated with ganglion cell death, reactive gliosis, and abortive regeneration. The second pattern of gene changes (23% of the variance) was primarily related to differences in gene expressions observed between the C57BL/6J and DBA/2J mouse strains. The remaining changes in gene expression represent interactions between the effects of optic nerve crush and the genetic background of the mouse. We extracted one genetic network from this dataset that appears to be related to tissue remodeling. One of the most intriguing sets of changes included members of the crystallin family of genes, which may represent a signature of pathways modulating the susceptibility of cells to death. Differential responses to optic nerve crush between two widely used strains of mice were used to define molecular networks associated with ganglion cell death and reactive gliosis. These results form the basis for our continuing interest in the modifiers of retinal injury. 18 Samples: 9 per strain (C57BL/6J & DBA/2J); 3 conditions per strain
Project description:We previously utilized interval-specific congenic lines derived from C57BL/6J (B6) and DBA/2J (D2) alleles to fine map a quantitative trait locus (QTL) influencing methamphetamine (MA)- induced locomotor activity. We identified a 0.23 MB critical interval on chromosome 11 containing only two protein coding genes, Rufy1 and Hnrnph1. Notably, Rufy1 contains three missense SNPs and Hnrnph1 contains 1 SNP near the 5’ UTR. In an effort to identify the molecular mechanisms that bridge genetic variation with behavior, we conducted transcriptome analysis via mRNA sequencing (RNA-seq) in a B6.D2 congenic line (chr.11: 50-60 Mb) that captures the QTL. There was an overrepresentation of cis-regulated, differentially expressed genes within the congenic interval (4 out of 92 differentially expressed genes; FDR < 0.05) and widespread genomic regulation on all autosomes.
Project description:Expression profiling of a cohort of mice was derived from a standard F2 intercross using two standard inbred strains, C57BL/6J and DBA/2J. In this study, we selected 127 male animals that had been raised on a standard rodent chow diet (Purina Chow from Ralston-Purina Co., St. Louis, MO) for eight weeks and then switched to a high fat diet for sixteen additional weeks. At 20 weeks of age, the mice were euthanized and liver tissues were collected and flash frozen in liquid nitrogen and stored at -80 degrees C prior to RNA isolation. All procedures of housing and treatment of animals were performed in accordance with IACUC regulations. RNA preparation and array hybridizations were performed at Rosetta Inpharmatics. The custom ink-jet microarrays were manufactured by Agilent Technologies (Palo Alto, CA). A custom array was designed for this study and consisted of 39,280 non-control oligonuceotides extracted from the mouse Unigene clusters and combined with RefSeq sequences and RIKEN full-length cDNA clones. Arrays were quantified on the basis of spot intensity relative to background, adjusted for experimental variation between arrays using average intensity over multiple channels, and fitted to a previously described error model to determine significance (type I error).
Project description:The pivotal role of stress in the precipitation of psychiatric diseases is generally accepted. To further elucidate the underlying molecular mechanisms, gene networks and signalling cascades, we investigated the impact of an acute stressor, forced swimming, on the gene expression profile in the hypothalamic paraventricular nucleus (PVN). We performed this study in C57BL/6J and DBA/2J mice, which are known to differ in their reaction to stress. Mice were exposed to forced swimming as stressor, brains were dissected 4h and 8h after stress, both from stressed and unstressed animals, and the RNA profiles from the PVN were evaluated by microarray analysis. Keywords: time course, treatment response, strain differences RNAs from unstressed animals (basal) were compared to RNAs from stressed animals (either 4h or 8h after stress) for both mouse strains (DBA/2J and C57BL/6). In addition, RNA from the two strains were compared under basal conditions. Technical replicates: 10 for each time point, including dye-swap each with 5 replicates