Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-Seq profiling of brain in Mucopolysaccharidosis type II mouse model

ABSTRACT: Lysosomal Storage Disorders (LSDs) are a group of about 50 metabolic disorders, sharing the inability to degrade specific endolysosomal substrates. This results in failure of cellular functions in many organ systems including brain in most patients, which show a progressive neurodegeneration. In this study we performed an RNA-Seq analysis of two brain areas (cerebral cortex and midbrain/diencephalon/hippocampus) of the mouse model for Mucopolysaccharidosis type II, a neurodegenerative LSD.

ORGANISM(S): Mus musculus

PROVIDER: GSE95224 | GEO | 2017/05/19

SECONDARY ACCESSION(S): PRJNA376439

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of normal and Mucopolysaccharidosis type VI rat fibroblast-like synoviocytes

Project description:Gene expression in 9 month-old Mucopolysaccharidosis type VI rat fibroblast-like synoviocytes (FLS) were compared to age-matched normal rat FLS

2007-10-24 | E-TABM-306 | biostudies-arrayexpress

Zebrafish models of Mucopolysaccharidosis types IIIA, B, & C show hyperactivity and changes in oligodendrocyte state

Project description:Sanfilippo syndrome childhood dementia, also known as mucopolysaccharidosis type III (MPS III), is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate (HS). An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete, and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs, nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH, NAGLU, and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA, B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS, while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal, glycosaminoglycan, immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA, B and C zebrafish, supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall, our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish’s extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA, B, and C subtypes.

2023-09-29 | GSE244310 | GEO

The Batten disease gene product CLN3 is required for the efflux of glycerophosphodiesters from lysosomes

Project description:The lysosome has many cellular roles, including degrading and recycling macromolecules and signaling to the mTORC1 growth regulator. Lysosomal dysfunction occurs in various human diseases, including common neurodegenerative diseases as well as monogenic lysosomal storage disorders (LSDs). For most LSDs the causal genes have been identified, but in many cases the function of the implicated gene is unknown. Here, we develop the LysoTag mouse line for the tissue-specific isolation of intact lysosomes that are compatible with the multimodal profiling of their contents. We apply it to the study of CLN3, a lysosomal transmembrane protein of unclear function whose loss causes juvenile neuronal ceroid lipofuscinosis (Batten disease), a lethal neurodegenerative LSD. Untargeted metabolite profiling of lysosomes from the brains of mice lacking CLN3 revealed a massive accumulation of glycerophosphodiesters (GPDs), the end products of glycerophospholipid catabolism. GPDs also accumulate in the lysosomes of CLN3-deficient cultured cells and stable isotope tracing experiments show that CLN3 is required for their lysosomal egress. Loss of CLN3 also alters upstream glycerophospholipid catabolism in the lysosome. Our results suggest that CLN3 is a lysosomal effluxer of GPDs and reveal Batten disease as the first, to our knowledge, neurodegenerative LSD with a primary defect in glycerophospholipid metabolism.

2022-07-11 | PXD018624 | Pride

lysosome proteomics in Niemann-Pick Type C disease model cells (CHOwt and NPC1-null cells)

Project description:Increasing evidence implicates lysosomal dysfunction in the pathogenesis of neurodegenerative diseases, including the rare inherited lysosomal storage disorders (LSDs) and the most common neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease (AD and PD). The goal of this work was to analyze whether there are changes in the lysosomal glycocalyx in a cellular model of a LSD Niemann-Pick type C disease (NPC). Using the ferrofluid nanoparticles we isolated lysosomal organelles from NPC1-null and CHOwt cells. Mass spectrometry identification of lysosomal proteins was performed in order to determine the enrichment efficiency for N-glycome profiling of the lysosomal glycocalyx in NPC disease cellular model.

2018-03-21 | PXD008438 | Pride

Molecular Profiling of Failed Endochondral Ossification in Mucopolysaccharidosis VII

Project description:Molecular Profiling of Failed Endochondral Ossification in Mucopolysaccharidosis VII

| PRJNA533818 | ENA

Proteomic analysis of mucopolysaccharidosis IIIB mouse brain

Project description:Mucopolysaccharidosis IIIB (MPS IIIB) is an inherited metabolic disease due to deficiency of ÃƒÅ½Ã‚Â±-N-Acetylglucosaminidase (NAGLU) enzyme with subsequent storage of undegradedheparan sulfate (HS). The main clinical manifestations of the disease are profound intellectual disability and neurodegeneration. To identify potential biomarkers and novel neuropathological mechanisms of MPS IIIB, a label-free quantitative proteomic approach was applied to compare the proteome profile of brains from MPS IIIB and control mice. Proteins were identified through a bottom up analysis and 130 were significantly under-represented and 74 over-represented in MPS IIIB mouse brains compared to wild type (WT). Multiple bioinformatic analyses of the differentially abundant proteins allowed to define three major clusters: proteins involved in cytoskeletal regulation, synaptic vesicle trafficking, and energy metabolism. The results highlight the involvement of these clustered proteins in the neuropathology of MPS IIIB disease. The proteins identified in this study would provide potential targets for diagnostic and therapeutic studies of MPS IIIB.

2020-02-26 | PXD017363 | Pride

Transcriptional impairments in mouse model of mucopolysaccharidosis IIIA and responses to systemic gene delivery using adeno-associated virus serotype rh74 vector (AAVrh74)

Project description:Mucopolysaccharidosis (MPS) IIIA is a neuropathic lysosomal storage disease caused by deficiency in SGSH. Genome-wide gene expression microarrays in MPS IIIA mice detected broad molecular abnormalities (≥2 fold, FDR≤10) in numerous transcripts (314) in the brain and blood (397). Importantly, 22 dysregulated blood transcripts are known to be enriched in the brain and linked to broad neuronal functions. To target the root cause, we used a self-complementary (sc) AAVrh74 vector to deliver the human SGSH gene into 4-6-wk-old MPS IIIA mice by an intravenous injection. The treatment resulted in global CNS and widespread somatic restoration of SGSH activity, clearance of CNS and somatic GAG storage, improved behavior performance, and significantly extended survival. The scAAVrh74-hSGSH treatment also led to the correction of the majority of the transcriptional abnormalities in the brain (95.9%) and blood (97.7%), of which 182 and 290 transcripts were normalized in the brain and blood, respectively. These results demonstrate that a single systemic scAAVrh74-hSGSH delivery mediated efficient restoration of SGSH activity and resulted in a near complete correction of MPS IIIA molecular pathology. This study also demonstrates that blood transcriptional profiles reflect the biopathological status of MPS IIIA, and also respond well to effective treatments.

2017-04-14 | GSE97759 | GEO

Lysosomal storage disease proteo/lipidomic profiling using nMOST links ferritinophagy with mitochondrial iron deficiencies in cells lacking NPC2

Project description:Lysosomal storage diseases (LSDs) comprised ~50 gene loci causing the accumulation of cellular material in the lysosome and associated defects in lysosomal function, but systematic molecular phenotyping is lacking. Here, we apply a nanoflow-based multi-omic single-shot technology (nMOST) workflow to simultaneously quantify HeLa cell proteomes and lipidomes from dozens of LSD mutants, revealing diverse molecular phenotypes. Defects in delivery of ferritin and its autophagic regulator NCOA4 to lysosomes (ferritinophagy) were pronounced in NPC2-/- cells, which correlated with increased lyso-phosphatidyl-choline species and dramatic multi-lamellar membrane structures visualized by cryo-electron tomography. Ferritinophagy defects correlated with loss of mitochondrial cristae, MICOS complex components, and electron transport chain complexes rich in iron-sulfur cluster proteins. Strikingly, these defects were rescued when iron was provided through the transferrin system. This resource reveals how loss of lysosomal function impacts organelle homeostasis in trans and highlights nMOST profiling as a discovery tool for illuminating distinct molecular phenotypes across LSDs.

2024-10-08 | PXD049336 | Pride

A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain [array]

Project description:We have undertaken the first comprehensive analysis of gene expression influenced by acute LSD administration in the mammalian brain to elucidate the mechanism of action of this class of drugs. We have identified a number of genes that are predicted to be involved in the processes of synaptic plasticity, glutamatergic signaling and cytoskeletal architecture. Understanding these molecular events will lead to new insights into the etiology of disorders whose behavioral symptoms resemble the temporary effects of hallucinogenic drugs, and also may ultimately result in new therapies.

2021-11-11 | GSE179378 | GEO

RNA-seq to investigate sex-dependent changes in microglia in Cst7 knockout mice crossed with a mouse model of amyloid-driven Alzheimer's Disease

Project description:Microglial endolysosomal dysfunction is strongly implicated in neurodegeneration. Transcriptomic studies show that a microglial state characterised by a set of genes involved in endolysosomal function is induced in both mouse Alzheimer’s Disease (AD) models and in human AD brain, and that the onset of this state is emphasised in females. Cst7 (Cystatin F) is among the most highly unregulated genes in these microglia. However, the sex-specific function of Cst7 in neurodegenerative disease is not understood. Here, we crossed Cst7 -/- mice with the App NL-G-F mouse to test the role of Cst7 in a model of amyloid-driven AD.

2023-11-22 | E-MTAB-13360 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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