RNA-seq analysis of RNA from DBA/2J retinal ganglion cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE90654 | GEO | 2017/03/07
SECONDARY ACCESSION(S): PRJNA355294
REPOSITORIES: GEO
Similar Datasets
Project description:Glaucoma is a common ocular disorder that is a leading cause of blindness worldwide. It is characterized by the dysfunction and loss of retinal ganglion cells (RGCs). Although many studies have implicated various molecules in glaucoma, no mechanism has been shown to be responsible for the earliest detectable damage to RGCs and their axons in the optic nerve. Here, we show that the leukocyte transendothelial migration pathway is activated in the optic nerve head at the earliest stages of disease in an inherited mouse model of glaucoma. This resulted in proinflammatory monocytes entering the optic nerve prior to detectable neuronal damage. A 1-time x-ray treatment prevented monocyte entry and subsequent glaucomatous damage. A single x-ray treatment of an individual eye in young mice provided that eye with long-term protection from glaucoma but had no effect on the contralateral eye. Localized radiation treatment prevented detectable neuronal damage and dysfunction in treated eyes, despite the continued presence of other glaucomatous stresses and signaling pathways. Injection of endothelin-2, a damaging mediator produced by the monocytes, into irradiated eyes, combined with the other glaucomatous stresses, restored neural damage with a topography characteristic of glaucoma. Together, these data support a model of glaucomatous damage involving monocyte entry into the optic nerve. Genome-wide assessment of gene expression changes was performed in DBA/2J-Gpnmb+, DBA/2J mice and irradiated DBA/2J mice at 8.5 and 10.5 months of age.
2012-03-28 | GSE36833 | GEO
Project description:In this study that was specifically designed to identify early stages of glaucoma in DBA/2J mice, we used genome-wide expression profiling and a series of computational methods. Our methods successfully subdivided eyes with no detectable glaucoma by conventional assays into molecularly defined stages of disease. These stages represent a temporally ordered sequence of glaucoma states. Using an array of tools, we then determined networks and biological processes that are altered at these early stages. Our strategy proved very sensitive, suggesting that similar approaches will be valuable for uncovering early processes in other complex, later-onset diseases. Early changes included upregulation of both the complement cascade and endothelin system, and so we tested the therapeutic value of separately inhibiting them. Mice with a mutation in the complement component 1a gene (C1qa) were robustly protected from glaucoma with the protection being among the greatest reported. Similarly, inhibition of the endothelin system was strongly protective. Since EDN2 is potently vasoconstrictive and was produced by microglial/macrophages, our data provide a novel link between these cell types and vascular dysfunction in glaucoma. Targeting early events such as the upregulation of the complement and endothelin pathways may provide effective new treatments for human glaucoma. Genome-wide assessment of gene expression changes was performed in DBA/2J mice. The optic nerve head and retina from 40 DBA/2J eyes at 10.5 months of age were separately profiled. These eyes were selected as they encompassed a range of glaucoma severity. Two control groups were also included; 10 eyes from 10.5 months old D2-Gpnmb+ mice (age and strain matched, no glaucoma control) and 10 eyes from 4.5 months old DBA/2J mice (young, pre-glaucoma).
2011-04-15 | E-GEOD-26299 | biostudies-arrayexpress
Project description:Purpose: The DBA/2J mouse is a model for secondary angle-closure glaucoma due to iris atrophy and pigment dispersion, which ultimately leads to increased intraocular pressure (IOP). We sought to correlate changes in retinal gene expression with glaucoma-like pathology by performing microarray analysis of retinal RNA from DBA/2J mice at 3 months before disease onset, and at 8 months, after IOP elevation. Methods: IOP was monitored monthly in DBA/2J animals by Tono-Pen and animals with normal (3 months) or elevated IOP (8 months) were identified. RNA was prepared from 3 individual retinas at each age, and the RNA was amplified and used to generate biotin-labeled probe for high density mouse Affymetrix arrays (U430.2). A subset of genes was selected for confirmation by quantitative RT-PCR using independent retina samples from DBA/2J animals at 3, 5 and 8 months of age, and compared to retinas from C57BL/6J control animals at 3 and 8 months. Results: There were changes in expression of 68 genes, with 32 genes increasing and 36 genes decreasing at 8 months versus 3 months. Upregulated genes were associated with immune response, glial activation, signaling and gene expression, while down-regulated genes included multiple crystallin genes. Significant changes in 9 upregulated genes and 2 downregulated genes were confirmed by quantitative RT-PCR, with some showing changes in expression by 5 months. Conclusions: DBA/2J retina shows evidence for glial activation and an immune-related response following IOP elevation, similar to what has been reported following acute elevation of IOP in other models. Keywords: retina, glaucoma, DBA/2J, elevated intraocular pressure
2005-11-04 | GSE3554 | GEO
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
2010-08-19 | E-GEOD-17117 | biostudies-arrayexpress
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.
2014-12-14 | E-GEOD-17810 | biostudies-arrayexpress
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.
2014-12-14 | GSE17810 | GEO
Project description:Genome sequencing of the DBA/2J strain of mouse
| PRJNA33589 | ENA
Project description:Mlycd encodes malonyl-CoA decarboxylase (MCD), which is an enzyme that localizes in the cytosolic, mitochondrial, and peroxisomal compartments and catalyzes the conversion of malonyl-CoA into acetyl-CoA. Malonyl-CoA can be converted into malonylcarnitine (C3DC). Patients with an autosomal recessive defect of MCD and MCD KO mice have pronounced elevations of C3DC. Analysis of plasma C3DC levels in the BxD genetic reference population revealed increased levels in BxD strains that harbor the DBA/2J haplotype at the site of the Mlycd gene. RNA sequencing was performed on two samples of DBA/2J mouse livers and two C57BL/6J mouse livers. Decreased expression of Mlycd gene as well as intronic reads in intron 2 were observed in DBA/2J livers. Long-read sequecing of DBA/2J livers in the Mlycd region confirmed an intracisternal A-particle (IAP) retrotransposon in intron 2 of the DBA/2J Mlycd sequence. To confirm the causal nature of the variant, DBA/2J mice with and without the C57BL/6J variant of Mlycd spliced in were tested for products of MCD enzymatic activity, and the C57BL/6J variant was able to rescue the phenotype seen in the DBA/2J mice.
2024-10-26 | GSE186973 | GEO
Project description:We hypothesize that gene expression in the CBs of these two strains of mice are divergent thus contributing to the disparity in the phenotypes. More specifically, (1) genes related to CB function are expressed less in the A/J mice compared to DBA/2J mice; (2) gene expression levels of morphogenic and trophic factors of the CB maybe significantly lower in the A/J mice than the DBA/2J mice. In order to test these hypotheses, we utilized microarray analysis to examine transcriptional differences between CBs of both strains of mice. Keywords: comparative expression profiling
2006-12-02 | GSE5313 | GEO
Project description:DBA/2J (D2) and C57BL/6J mice (B6) were infected intra-nasally with 2x10^3 FFU of influenza A H1N1 (PR8) virus. Lungs were collected from mock-infected controls or at day 1,2,3,4 post infection. Expression data were obtained from three independent experiments. We infected a highly susceptible mouse strain (D2) and a resistant strain (B6) with PR8 and performed a genome-wide expression analysis. We found genes expressed in lung epithelium that were specifically down-regulated in D2 mice, whereas a cluster of genes on chromosome 3 was only down-regulated in B6. In both mouse strains, chemokines, cytokines and interferon-response genes were up-regulated, indicating that the main innate immune defense pathways were activated. However, many immune response genes were up-regulated in D2 much stronger than in B6, and several immune response genes were exclusively regulated in D2. Thus, susceptible D2 mice showed a hyper-inflammatory response. This response is similar to infections with highly pathogenic influenza virus and may serve as a paradigm for a hyper-inflammatory host response to influenza A virus.
2011-12-01 | E-MTAB-835 | biostudies-arrayexpress