Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

52 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Progesterone Antagonist Therapy in a Pelizaeus-Merzbacher Mouse Mode

ABSTRACT: Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disease, characterized by ataxia, intellectual disability, epilepsy and premature death. In the majority of cases, PMD is caused by duplication of PLP1 that is expressed in myelinating oligodendrocytes. Despite detailed knowledge of PLP1, there is presently no curative therapy for PMD. We used a Plp1 transgenic PMD mouse model to test the therapeutic effect of Lonaprisan, an antagonist of the nuclear progesterone receptor, in lowering Plp1 mRNA overexpression. We applied placebo-controlled Lonaprisan therapy to PMD mice for 10 weeks and performed the grid slip analysis to assess the clinical phenotype. Additionally, mRNA expression and protein accumulation as well as histological analysis of the central nervous system were performed. While Plp1 mRNA levels are increased about 1.8-fold in PMD mice compared to wildtype controls, daily Lonaprisan treatment reduced overexpression at the RNA level up to 1.5-fold, which was sufficient to significantly improve a poor motor phenotype. Electron microscopy confirmed a 25% increase in the number of myelinated axons in the corticospinal tract when compared to untreated PMD mice. Microarray analysis revealed the upregulation of pro-apoptotic genes in PMD mice that could be partially rescued by Lonaprisan treatment, which also reduced microgliosis, astrogliosis, and lymphocyte infiltration. We treated mice with Lonaprisan or vehicle for 10 weeks. Brains from 13 week old mice were collected and subsequently lysed for total RNA extraction. We took three biological replicates for each Treatment and Placebo.

ORGANISM(S): Mus musculus

SUBMITTER: Sven Wichert

PROVIDER: E-GEOD-55315 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Progesterone Antagonist Therapy in a Pelizaeus-Merzbacher Mouse Mode

Project description:Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disease, characterized by ataxia, intellectual disability, epilepsy and premature death. In the majority of cases, PMD is caused by duplication of PLP1 that is expressed in myelinating oligodendrocytes. Despite detailed knowledge of PLP1, there is presently no curative therapy for PMD. We used a Plp1 transgenic PMD mouse model to test the therapeutic effect of Lonaprisan, an antagonist of the nuclear progesterone receptor, in lowering Plp1 mRNA overexpression. We applied placebo-controlled Lonaprisan therapy to PMD mice for 10 weeks and performed the grid slip analysis to assess the clinical phenotype. Additionally, mRNA expression and protein accumulation as well as histological analysis of the central nervous system were performed. While Plp1 mRNA levels are increased about 1.8-fold in PMD mice compared to wildtype controls, daily Lonaprisan treatment reduced overexpression at the RNA level up to 1.5-fold, which was sufficient to significantly improve a poor motor phenotype. Electron microscopy confirmed a 25% increase in the number of myelinated axons in the corticospinal tract when compared to untreated PMD mice. Microarray analysis revealed the upregulation of pro-apoptotic genes in PMD mice that could be partially rescued by Lonaprisan treatment, which also reduced microgliosis, astrogliosis, and lymphocyte infiltration.

2014-02-26 | GSE55315 | GEO

Enteric glia express proteolipid protein 1 and are a transcriptionally unique population of glia in the mammalian nervous system

Project description:To identify the gene expression profile of enteric glia and assess the transcriptional similarity between enteric and extraenteric glia, we performed RNA sequencing analysis on PLP1-expressing cells in the mouse intestine. This analysis shows that enteric glia are transcriptionally unique and distinct from other cell types in the nervous system. Enteric glia express many genes characteristic of the myelinating glia, Schwann cells and oli- godendrocytes, although there is no evidence of myelination in the murine ENS. Total RNA expression profiles of PLP1 expressing enteric glial cells (GFP+) and non-glial cells (GFP-negative) were obtained from the ileum and colon of juvenile PLP1-eGFP transgenic mice.

2015-09-01 | E-GEOD-72560 | biostudies-arrayexpress

mRNA microarray analysis of the substantia nigra in a mouse model of multiple system atrophy

Project description:Multiple system atrophy (MSA) is a fatal rapidly progressive Î±-synucleinopathy, characterized by prominent Î±-synuclein accumulation in oligodendrocytes. In this study we investigated mRNA expression in substantia nigra of MSA transgenic mice (Tg(Plp1-SNCA)1Haa) and wild type controls. This forms part of a larger study in which we investigated miRNA-mRNA regulatory network in substantia nagra and striatum of MSA transgenic mice in pre-motor stage of neurodegenration.

2016-03-15 | E-MTAB-3985 | biostudies-arrayexpress

microRNA profiling by high-throughput sequencing in the substantia nigra and striatum of Multiple System Atrophy (MSA) transgenic mice and wild type controls

Project description:Multiple system atrophy (MSA) is a fatal rapidly progressive Ia-synucleinopathy, characterized by prominent Ia-synuclein accumulation in oligodendrocytes. In this study we investigated miRNA expression in the substantia nigra and striatum of MSA transgenic mice (Tg(Plp1-SNCA)1Haa) and wild type controls. This forms part of a larger study in which we investigated miRNA-mRNA regulatory network in substantia nigra and striatum of MSA transgenic mice in pre-motor stage of neurodegenration.

2016-03-15 | E-MTAB-3993 | biostudies-arrayexpress

Modeling the mutational and phenotypic landscapes of Pelizaeus-Merzbacher Disease using human iPSC-derived oligodendrocytes

Project description:Pelizaeus-Merzbacher disease (PMD) is a pediatric disease of myelin in the central nervous system and manifests with a wide spectrum of clinical severities. Although PMD is a rare monogenic disease, hundreds of mutations in the X-linked myelin gene proteolipid protein 1 (PLP1) have been identified in humans. Attempts to identify a common pathogenic process underlying PMD have been complicated by an incomplete understanding of PLP1 dysfunction and limited access to primary human oligodendrocytes. To address this, we generated panels of human induced pluripotent stem cells (hiPSCs) and hiPSC-derived oligodendrocytes from 12 individuals with mutations spanning the genetic and clinical diversity of PMD—including point mutations and duplication, triplication, and deletion of PLP1—and developed an in vitro platform for molecular and cellular characterization of all 12 mutations simultaneously. We identified individual and shared defects in PLP1 mRNA expression and splicing, oligodendrocyte progenitor development, and oligodendrocyte morphology and capacity for myelination. These observations enabled classification of PMD subgroups by cell-intrinsic phenotypes and identified a subset of mutations for targeted testing of small-molecule modulators of the endoplasmic reticulum stress response, which improved both morphologic and myelination defects. Collectively, these data provide insights into the pathogeneses of a variety of PLP1 mutations and suggest that disparate etiologies of PMD could require specific treatment approaches for subsets of individuals. More broadly, this study demonstrates the versatility of a hiPSC-based panel spanning the mutational heterogeneity within a single disease and establishes a widely applicable platform for genotype-phenotype correlation and drug screening in any human myelin disorder.

2017-04-04 | GSE96049 | GEO

miRNA microarray analysis of the substantia nigra and stratum in a mouse model of multiple system atrophy

Project description:Multiple system atrophy (MSA) is a fatal rapidly progressive Î±-synucleinopathy, characterized by prominent Î±-synuclein accumulation in oligodendrocytes. In this study we used Exiqon microarrays to investigate micro RNA expression in substantia nigra and striatum of MSA transgenic mice (Tg(Plp1-SNCA)1Haa) and wild type controls. This forms part of a larger study in which we investigated miRNA-mRNA regulatory network in substantia nagra and striatum of MSA transgenic mice in pre-motor stage of neurodegenration.

2016-03-15 | E-MTAB-3986 | biostudies-arrayexpress

High-resolution custom array spanning Xq22 region to study patients carrying PLP1 copy number gain

Project description:We investigated the features of the genomic rearrangements in a cohort of 50 male individuals with proteolipid protein 1 (PLP1) copy number gain events who were ascertained with Pelizaeus-Merzbacher disease (PMD; MIM: 312080). Genomic rearrangements in PMD individuals with PLP1 copy number gain events were investigated by high-density customized array and breakpoint junction sequence analysis. Analysis of these data enabled the spectrum and relative distribution of the underlying genomic mutational signatures to be delineated. Genomic rearrangements in PMD individuals with PLP1 copy number gain events were investigated by high-density customized array and breakpoint junction sequence analysis.

2019-10-09 | GSE138542 | GEO

Differentially expressed genes among motor and prefrontal areas of macaque monkey neocortex

Project description:Motor-related areas of neocortex are highly differentiated into several subareas from both functional and cytoarchitectural aspects in the higher primates. To assess the molecular basis of such areal specialization, we investigated the gene expression profiles of primary motor area (M1), premotor area (dorsal and ventral) (PMd and PMv) and prefrontal area (A46) in the rhesus monkey by DNA microarray method. We found that 476 genes were differentially expressed among those areas. More than half of those genes were most abundantly expressed in M1, and most genes were complementarily expressed between M1 and A46. The expression profiles of PMd and PMv were similar to each other compared to those of M1 and A46. The data will give us a fundamental basis for further analysis of structure-function relationship of the primate brain. Keywords: cerebral neocortex; rhesus monkey; primary motor area; premotor area; prefrontal area Twenty four brain tissues from 4 areas (M1, PMd, PMv and A46) of right and left hemispheres of 3 adolescent rhesus monkeys (Macaca mulatta) aged 2.6-2.7 years which had been bred in group cages without any experimental treatments. Adequate measures were taken to minimize pain and discomfort, in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH publication no. 80-23).

2007-08-31 | E-GEOD-8644 | biostudies-arrayexpress

mRNA expression data from mice infected with H. pylori treated with estradiol, tamoxifen, or placebo

Project description:We are investigating the mRNA expression profiles of gastric tissue within H. pylori-infected mice treated with estradiol, tamoxifen, or placebo We used microarrays to compare the global mRNA expression profiles in H. pylori infected mice in response to estradiol and tamoxifen Male mice were infected with H. pylori. After 16 weeks of H.pylori infection, mice were treated with 17beta-estradiol, Tamoxifen or placebo pellets implated subcutaneously for 12 weeks. At that point, longitudinal strips of gastric tissue were snap-frozen. Tissue was later weighed and RNA extracted using Trizol and purified with RNeasy kit including DNase treatment. 9 samples with 3 groups (n= 3 per group, except Tamoxifen (n=2)). Placebo samples are controls and were compared to estradiol or Tamoxifen treated samples.

2011-06-30 | E-GEOD-29715 | biostudies-arrayexpress

Complex Genomic Rearrangements at the PLP1 Locus Include Triplication and Quadruplication

Project description:Inverted repeats (IRs) can facilitate structural variation as crucibles of genomic rearrangement. Complex DUP-TRP/INV-DUP rearrangements that contain breakpoint junctions within IRs have been recently associated with both MECP2 duplication syndrome (MIM#300260) and Pelizaeus-Merzbacher disease (PMD, MIM#312080). We investigated 17 unrelated PMD subjects with copy number gains at the PLP1 locus including triplication and quadruplication of specific genomic intervals M-bM-^@M-^S 16/17 were found to have a DUP-TRP/INV-DUP rearrangement product. An IR distal to PLP1 facilitates DUP-TRP/INV-DUP formation as well as an inversion structural variation found frequently amongst normal individuals. We show that a homologyM-bM-^@M-^Tor homeologyM-bM-^@M-^Tdriven replicative mechanism of DNA repair can apparently mediate template switches within stretches of microhomology. Moreover, we provide evidence that quadruplication, and potentially higher order amplification of a genomic interval, can occur in a manner consistent with rolling circle amplification as predicted by the microhomology mediated break induced replication (MMBIR) model. To determine size, genomic extent and gene content for each rearrangement, we used a customized tiling-path oligonucleotide microarray spanning the Xq22 chromosomal region to query the genomic DNA of 7 males with Pelizaeus-Merzbacher disease, and 5 unaffected or carrier/unaffected family members. A 4x44k Agilent Technologies (Santa Clara, CA) microarray was designed using the Agilent e-array website targeting the region of the genome encompassing the dosage-sensitive PLP1 gene.

2014-11-25 | E-GEOD-63594 | 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