Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptomic analysis of DJ-1 knockout rat brains using RNA-Seq

ABSTRACT: Mutations in the DJ-1 gene cause rare forms of autosomal recessive Parkinson's disease in humans. Recently, DJ-1 knockout rats have been generated and they have been reported to have subtle motor defects and neurodegeneration. We hypothesized that measuring the differences in mRNA expression in the brains of wildtype and DJ-1 knockout rats would provide insight into the mechanisms underlying these phenotypes. Using RNA-Seq, we were able to measure differential expression of over 2,000 genes in the DJ-1 knockout rat brains.

ORGANISM(S): Rattus rattus

PROVIDER: GSE71968 | GEO | 2017/09/11

SECONDARY ACCESSION(S): PRJNA292611

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

iTRAQ Analysis of DJ-1 Knockout Rodent Brains

Project description:Mutations in the DJ-1 (Park7) gene cause autosomal recessive Parkinson's disease in humans, but the function of the DJ-1 protein is poorly characterized. In an effort to understand more about the biology of DJ-1, we performed iTRAQ analyses on subcellular fractions enriched from DJ-1 knockout rat and mouse brains. We generated iTRAQ datasets for mitochondria and cytosol enriched fractions from 6-month-old rat brains, and the cytosol enriched fraction from 14-15-month old mouse brains. Our subsequent analyses of these datasets led to our discovery that the Hexokinase 1 protein was increased in the cytosol components of both DJ-1 knockout species.

2017-10-04 | PXD005215 | Pride

Analysis of DJ-1 Knockout Mouse Brains

Project description:We analyzed metabolites in the brains of wild type mice and DJ-1 knockout mice. The DJ-1 knockout mouse is a model of an inherited form of Parkinson's disease.

2015-09-17 | ST000260 | MetabolomicsWorkbench

Transcriptomic analysis of dj-1-/- zebrafish brains compared to wild type siblings

Project description:RNA-Seq comparing transcript expression in the brains of 3 dj-1-/- mutant zebrafish and 3 wild type siblings at 16 weeks post fertilisation.

2019-08-02 | GSE135271 | GEO

RNA binding activity of the recessive parkinsonism protein DJ-1

Project description:Parkinson disease (PD) is a major neurodegenerative condition with several rare Mendelian forms. Oxidative stress and mitochondrial function have been implicated in the pathogenesis of PD but the molecular mechanism(s) involved in the degeneration of specific neuronal groups remains unclear. DJ-1 mutations are one cause of recessive parkinsonism, but this gene is also involved in cancer by promoting Ras signaling and suppressing PTEN-induced apoptosis. The specific function of DJ-1 is unclear, although it is responsive to oxidative stress and may play a role in the maintenance of mitochondria. Here we show that DJ-1 associates with specific RNA targets in cells and in the brain including mitochondrial genes, genes involved in glutathione metabolism and members of the PTEN/PI3K cascade. Pathogenic recessive mutants are deficient in this activity. We show that DJ-1 is sufficient for RNA binding at nanomolar concentrations in vitro and that there is some RNA sequence specificity to the association. Oxidative stress causes DJ-1 to dissociate from RNA. Using in vitro and in vivo models of mild oxidative stress, we show that DJ-1 normally suppresses translation in normal circumstances but allows translation after oxidative stress. We tested the hypothesis that these specific RNA targets are responsible for sensitivity to stress by exposing knockout flies to glutathione synthesis inhibitors and saw the predicted increased sensitivity in vivo. These data implicate a single mechanism for the pleiotropic effects of DJ-1 in different model systems, namely that the protein binds and regulates specific groups of RNA targets in an oxidationdependent manner. Furthermore, these results suggest how a small protein might both be an upstream regulator of processes important in parkinsonism and be a modifier of cancer-related processes. Keywords: Immunoprecipitated RNA comparisons

2008-03-14 | GSE8632 | GEO

A novel splicing variant of DJ-1 specific to Parkinson’s disease induces mitochondrial dysfunction

Project description:We characterize differentially spliced genes in postmortem human substantia nigra samples derived from various disease conditions, and discover a novel Parkinson's disease-associated splice variant, DJ-1 lacking exon 6.

2023-02-26 | GSE206961 | GEO

PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis during ageing

Project description:Pyruvate dehydrogenase (PDH) is the gatekeeper enzyme of the tricarboxylic acid (TCA) cycle. Here we show that the deglycase DJ-1 (encoded by PARK7, a key familial Parkinson's disease gene) is a pacemaker regulating PDH activity in CD4+ regulatory T cells (Treg cells). DJ-1 binds to PDHE1-β (PDHB), inhibiting phosphorylation of PDHE1-α (PDHA), thus promoting PDH activity and oxidative phosphorylation (OXPHOS). Park7 (Dj-1) deletion impairs Treg survival starting in young mice and reduces Treg homeostatic proliferation and cellularity only in aged mice. This leads to increased severity in aged mice during the remission of experimental autoimmune encephalomyelitis (EAE). Dj-1 deletion also compromises differentiation of inducible Treg cells especially in aged mice, and the impairment occurs via regulation of PDHB. These findings provide unforeseen insight into the complicated regulatory machinery of the PDH complex. As Treg homeostasis is dysregulated in many complex diseases, the DJ-1-PDHB axis represents a potential target to maintain or re-establish Treg homeostasis.

2022-04-19 | GSE115269 | GEO

Transcriptomic analysis of dj-1-/- zebrafish brains compared to wild type siblings

Project description:Transcriptomic analysis of dj-1-/- zebrafish brains compared to wild type siblings

| PRJNA558074 | ENA

DJ-1 depletion prevents immunoaging in T-cell compartments

Project description:Decline in immune function during aging increases susceptibility to different aging related diseases. However, the underlying molecular mechanisms, especially the genetic factors contributing to imbalance of naïve/memory T-cell subpopulations, still remain largely elusive. Here we show that loss of DJ-1 encoded by PARK7/DJ-1, causing early-onset familial Parkinson’s disease (PD), unexpectedly diminished signs of immunoaging in T-cell compartments of both human and mice. Compared with two gender-matched unaffected siblings of similar ages, the index PD patient with DJ-1 deficiency showed a decline in many critical immunoaging features, including almost doubled non-senescent T cells. The observation was further consolidated by the results in 45-week-old DJ-1 knockout mice. Our data demonstrated that DJ-1 regulates several immunoaging features via hematopoietic-intrinsic and naïve-CD8-intrinsic mechanisms. Mechanistically, DJ-1 depletion reduced oxidative phosphorylation (OXPHOS) and impaired TCR sensitivity in naïve CD8 T cells at a young age, accumulatively leading to a reduced aging process in T-cell compartments in older mice. Our finding suggests an unrecognized critical role of DJ-1 in regulating immunoaging, discovering a potent target to interfere with immunoaging- and aging-associated diseases.

2022-01-17 | GSE173904 | GEO

DJ-1 governs airway progenitor cell/eosinophil interactions to promote allergic inflammation

Project description:Background DJ-1 is an antioxidant protein known to regulate mast cell mediated allergic response, but its role in airway eosinophilic interactions and allergic inflammation is not known. Objective The aim of this study was to investigate the role of DJ-1 in airway eosinophilic inflammation in vitro and in vivo. Methods Ovalbumin-induced airway allergic inflammation was established in mice. ELISA was adopted to analyze DJ-1 and cytokine levels in mouse bronchoalveolar lavage fluid. Transcriptional profiling of mouse lung tissues was conducted by single-cell RNA sequencing technology. The role of DJ-1 in the differentiation of airway progenitor cells into goblet cells was examined by organoid cultures, immunofluorescence staining, quantitative PCR, and cell transplantation in normal, DJ-1 knockout (KO), or conditional DJ-1 KO mice. Results We observed that DJ-1 was increased in the lung tissues of ovalbumin-sensitized and challenged mice. DJ-1 KO mice exhibited reduced airway eosinophil infiltration and goblet cell differentiation. Mechanistically, we discovered that eosinophil-club cell interactions are reduced in the absence of DJ-1. Organoid cultures indicated that eosinophils impair the proliferative potential of club cells. Intratracheal transplantation of DJ-1-deficient eosinophils suppresses airway goblet cell differentiation. Loss of DJ-1 inhibits the metabolism of arachidonic acid into cysteinyl leukotrienes in eosinophils while these secreted metabolites promote airway goblet cell fate in organoid cultures and in vivo. Conclusion DJ-1-mediated interactions between airway epithelial progenitor cells and immune cells are essential in controlling airway goblet cell metaplasia and eosinophilia. Blockade of the DJ-1 pathway is protective against airway allergic inflammation.

2022-12-21 | GSE203079 | GEO

Skeletal muscle-specific DJ-1 ablation-induced atrogenes expression and mitochondrial dysfunction contributing to muscular atrophy

Project description:DJ-1 is a causative gene for a familial form of Parkinson disease. DJ-1 deficient mice develop progressive behavioral abnormalities in gaits and forearm grip strength are hypoactive. The mechanisms under the activity are not fully known. Here we show that DJ-1 is critical for disuse- induced skeletal muscle atrophy. Firstly, DJ-1 expression is positively correlated with muscle mass in human, and is decreased in atrophy muscle of immobilization mice and aged human. Secondly, DJ-1-deficient muscles are dystrophic, as well as impaired in activities and oxidative capacity. In disuse-atrophic condition, skeletal muscle specific-DJ-1 knockout mice show less cross section area (CSA) and more central nuclei than control mice. Thirdly, biochemical analysis indicates that these changes are due to enhanced activation of FoxO1, and subsequent upregulation of atrogenes. Finally, the inhibitor of DJ-1, compound 23, can mimic the effects of DJ-1 ablation in vivo. Our results illuminate that skeletal muscle DJ-1 has an unexpected role in the regulation of catabolic signals from mechanical stimulation, providing a therapeutic target for muscle-wasting diseases.

2023-12-12 | GSE216408 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data