Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Global gene expression change in the cerebellum of Niemann-Pick disease type C mice with deletion of Ccl3 or Purkinje neuron-specific NPC1 rescue

ABSTRACT: Macrophage inflammatory protein 1alpha/CCL3 protein is a known pro-inflammatory cytokine that can mediate chemotaxis of monocytes and promote cell degranulation. Ccl3 gene expression is elevated in the CNS and visceral tissue of many lysosomal storage disorders. The deletion of Ccl3 in a mouse model of Sandhoff disease was reported to result in reduced monocyte-associated pathology in the brain, delayed neurodegeneration, and prolonged health. However, deletion of Ccl3 in a mouse model of Niemann-Pick C disease was dentrimental or neutral instead of beneficial. Prevention of neuronal loss was instead mediated by providing NPC1 to neurons. We used microarrays to detail the global change in gene expression of the cerebellum in Niemann-Pick C disease animals, Niemann-Pick C disease animals with Ccl3 gene deletion, and Niemann-Pick C disease animals with Purkinje neuron-specific NPC1-YFP rescue.

ORGANISM(S): Mus musculus

PROVIDER: GSE36119 | GEO | 2012/04/17

SECONDARY ACCESSION(S): PRJNA152925

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Global gene expression change in the cerebellum of Niemann-Pick disease type C mice with deletion of Ccl3 or Purkinje neuron-specific NPC1 rescue

Project description:Macrophage inflammatory protein 1alpha/CCL3 protein is a known pro-inflammatory cytokine that can mediate chemotaxis of monocytes and promote cell degranulation. Ccl3 gene expression is elevated in the CNS and visceral tissue of many lysosomal storage disorders. The deletion of Ccl3 in a mouse model of Sandhoff disease was reported to result in reduced monocyte-associated pathology in the brain, delayed neurodegeneration, and prolonged health. However, deletion of Ccl3 in a mouse model of Niemann-Pick C disease was dentrimental or neutral instead of beneficial. Prevention of neuronal loss was instead mediated by providing NPC1 to neurons. We used microarrays to detail the global change in gene expression of the cerebellum in Niemann-Pick C disease animals, Niemann-Pick C disease animals with Ccl3 gene deletion, and Niemann-Pick C disease animals with Purkinje neuron-specific NPC1-YFP rescue. To identify the top ~50 genes elevated in NPC disease Npc1-/- (NPC) and Npc1+/- (WT) mice were compared at age P50; To profile changes in gene expression as a result of Ccl3 gene deletion Ccl3-/-;Npc1-/- mice were compared against Npc1-/- mice across various ages; To profile changes in gene expression as a result of Purkinje neuron-sepcific NPC1 rescue P;N;Npc1-/- mice were compared against Npc1-/- mice across various ages.

2012-04-16 | E-GEOD-36119 | biostudies-arrayexpress

Proteomic analysis of monocyte derived macrophages from Niemann-Pick disease type C patients

Project description:Niemann-Pick type C disease is a rare neurodegenerative disorder mainly caused by mutations in Npc1, resulting in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is a prominent pathological feature, direct consequences of NPC1 loss on microglial function remain uncharacterized. Previously, we have characterized microglial proteome alterations in the NPC1 KO mouse model (PXD019447). In order to investigate similar changes in humans, we have cultured monocyte derived macrophages of NPC1 patients and control donors.

2021-02-09 | PXD020659 | Pride

CHEMICAL PROTEOMIC ANALYSIS OF ENDOCANNABINOID HYDROLASE ACTIVITY IN NIEMANN-PICK TYPE C MOUSE BRAIN

Project description:The endocannabinoid system is considered to be an endogenous protective system in various neurodegenerative diseases. Niemann-Pick Type C is a neurodegenerative disease in which the role of the endocannabinoid system has not been studied yet. Here, we report the endocannabinoid hydrolase activity in brain proteomes of a Niemann-Pick type C mouse model as measured by activity-based protein profiling. Diacylglycerol lipase α, α/β-hydrolase domain-containing protein 4 (ABHD4), ABHD6, ABHD12, fatty acid amide hydrolase and monoacylglycerol lipase activities were quantified. Chemical proteomics showed no difference in endocannabinoid hydrolase activity in the brain of wildtype compared to Niemann-Pick C1 protein (NPC1) knockout mice. Three lysosomal serine hydrolases were identified with increased activity in NPC1 knockout mouse brain: retinoid-inducible serine carboxypeptidase, cathepsin A and palmitoyl-protein thioesterase 1, and we conclude that these might be interesting therapeutic targets for future validation studies.

2018-04-19 | PXD008979 | Pride

Quantitative proteomics of human NPC1-I1061T mutant fibroblasts provides insights into the pathogenesis of Niemann-Pick Type C disease

Project description:Niemann-Pick type C (NPC) disease is a fatal neurodegenerative disorder characterized by the accumulation of unesterified cholesterol in the late endosomal/lysosomal compartments. Mutations in the NPC1 protein are implicated in 95% of patients with NPC disease. The most prevalent mutation is the missense mutation I1061T that occurs in approximately 15–20% of disease alleles. In this study, we have performed an isobaric labeling based quantitative analysis of proteome of NPC1-I1061T versus wild-type primary fibroblasts.

2015-04-20 | PXD001938 | Pride

The role of Niemann-Pick type C2 in zebrafish embryonic development

Project description:Niemann-Pick disease type C (NPC) is a rare fatal neurodegenerative lysosomal storage disease caused by mutations of either NPC1 or NPC2. NPC2 is a soluble lysosomal protein that in coordination with NPC1 is responsible for the efflux of unesterified cholesterol from the lysosome. Mutations of both genes cause a similar cellular pathology, that includes the accumulation of unesterified cholesterol and other lipids in the late endosome/lysosome, while reducing cholesterol bioavailability. Here we describe a npc2 null zebrafish model generated by CRISPR/Cas9 gene targeting. Zygotic npc2m/m zebrafish from the intercross of npc2+/m individuals showed significant unesterified cholesterol accumulation at larval stages, and a reduction in body size in adulthood. Additionally, zygotic npc2m/m adults exhibited motor and balance defects shortly before a premature death. These findings mimic defects found in human and mice, however the phenotype at embryonic stages were milder than expected. To address the possible dose protection effects of npc2 mRNA present in the oocyte at the time of fertilization we intercrossed npc2m/m zebrafish to generate Maternal-zygotic (MZ) npc2m/m embryos. MZnpc2m/m zebrafish exhibited significant developmental defects including absent otolith, abnormal head/brain development, curved/twisted body axis, no circulating blood cells, and died by 72 hpf. These developmental defects have not previously been reported in connection with either NPC2 or NPC1. RNA-seq analysis conducted on 30 hpf npc2+/m and MZnpc2m/m embryos revealed a significant reduction in notch3 expression as well as reduction in other downstream genes in the signally pathway such as hey1 and her12 that could be partially rescued by microinjection of a plasmid containing the constitutively active notch3 ICD at the 1-cell stage, suggesting that impaired Notch3 signaling likely underlies some aspects of the developmental defects observed in MZnpc2m/m zebrafish.

2021-03-20 | GSE161867 | GEO

Niemann-Pick type C fibroblast analysis

Project description:Primary skin fibroblasts from four Niemann-Pick type C patients homozygous for the I1061T mutation and four control individuals were cultured under identical conditions in DMEM containing 10% fetal bovine serum. Cells were harvested at 50-70% confluency. mRNA was isolated with the FastTrack 2.0 mRNA isolation kit according to the manufacturer's instructions (Invitrogen, Carlsbad, CA). A reference RNA comprised of 10 cell lines was used as the control for each hybridized sample (Stratagene, La Jolla, CA). Both sample and reference RNAs were amplified using the MessageAmp II aRNA amplification kit (Ambion, Austin, TX). Set of arrays that are part of repeated experiments Biological Replicate Complex

2007-08-15 | E-GEOD-8770 | biostudies-arrayexpress

Differential gene expression in BALB/c Npc1-/- and Npc1+/+ cerebellum

Project description:Purkinje cells (PC) of the cerebellum degenerate in adult mice with mutations in the Niemann-Pick type C (NPC) disease 1 (Npc1) gene. We subjected BALB/c Npc1+/+ and Npc1-/- mouse cerebella from an early and a later time point of PC degeneration to a genome-wide microarray gene expression analysis. We found general underrepresentation of PC-specific transcripts, consistent with PC loss, and elevated markers of microglia activation at the later time point. Keywords: Niemann-Pick type C, Purkinje cell degeneration

2007-07-01 | GSE5944 | GEO

Niemann-Pick type C fibroblast analysis

2007-08-15 | GSE8770 | GEO

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

Human iNSC-derived brain organoid model of lysosomal storage disorder in Niemann-Pick disease type C

Project description:Recent studies on developing three-dimensional (3D) brain organoids from stem cells have allowed the generation of in vitro models of neural disease and have enabled the screening of drugs because these organoids mimic the complexity of neural tissue. Niemann-Pick disease, type C (NPC) is a neurodegenerative lysosomal storage disorder caused by mutations in the NPC1 protein. The pathological features underlying NPC are characterized by the abnormal accumulation of cholesterol in acidic compartments, including late endosomes and lysosomes. Due to the inaccessibility of brain tissues from human NPC patients, we developed NPC brain organoids with induced neural stem cells from NPC patient-derived fibroblasts. NPC organoids exhibit significantly reduced size and proliferative ability, which are accompanied by accumulation of cholesterol, impairment in neuronal differentiation and autophagic flux and dysfunction of lysosomes; therefore, NPC organoids can recapitulate the main phenotypes of NPC patients. Furthermore, these pathological phenotypes observed in NPC organoids were reversed by treatment with valproic acid, which is known to be an effective treatment for several neurodegenerative diseases. Our data present patient-specific phenotypes in 3D organoid-based models of NPC and highlight the application of this model to drug screening in vitro.

2020-12-21 | GSE157676 | GEO

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