Rattus norvegicus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA325596 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3664150_1.fastq.gz | Fastqsanger.gz | |||
| SRR3664150_2.fastq.gz | Fastqsanger.gz | |||
| SRR3664151_1.fastq.gz | Fastqsanger.gz | |||
| SRR3664151_2.fastq.gz | Fastqsanger.gz | |||
| SRR3664152_1.fastq.gz | Fastqsanger.gz |
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Project description:Rett syndrome is a human intellectual disability disorder that is associated with mutations in the X-linked MECP2 gene. Theepigenetic reader MeCP2 binds to methylated cytosines on the DNA and regulates chromatin organization. We have shownpreviously that MECP2 Rett syndrome missense mutations are impaired in chromatin binding and heterochromatinreorganization. Here, we performed a proteomics analysis of post-translational modifications of MeCP2 isolated from adult mousebrain. We show that MeCP2 carries various post-translational modifications, among them phosphorylation on S80 and S421, whichlead to minor changes in either heterochromatin binding kinetics or clustering. We found that MeCP2 is (di)methylated on severalarginines and that this modification alters heterochromatin organization. Interestingly, we identified the Rett syndrome mutationsite R106 as a dimethylation site. In addition, co-expression of protein arginine methyltransferases 1 and 6 lead to a decrease ofheterochromatin clustering. Altogether, we identified and validated novel modifications of MeCP2 in the brain and show that thesecan modulate its ability to bind as well as reorganize heterochromatin, which may play a role in the pathology of Rett syndrome.
2022-10-15 | PXD033696 | Pride
Project description:Rett syndrome is a severe neurodevelopmental condition that rsults primarily from mutations in the MECP2 gene. MECP2 is known to function as both a transcriptional activator and transcriptional repressor. However, it remains unclear how transcriptional dysregulation resulting from MECP2 mutations lead to the Rett syndrome phenotype. Multiple mouse models have been generated to investigate the function of MECP2 in vivo. Remarkably, despite the neurodevelopmental phenotype characteristic of Rett syndrome, temporal conditional MECP2 knock-out mouse models with MECP2 deletion induced postnatally recapitulate the Rett-syndrome-like phenotype in mouse. Here we investigated gene expression changes in 22-weeks old mice following conditional MECP knock-out at 12 weeks by RNA-sequencing. Consistent with previous data, we identify mild gene expression changes following MECP2 knock-out. These data could prove valuable in future studies comparing conditional MECP2 knock-out at distinct time points and in additional brain regions, and can also serve for investigating alternative splicing changes resulting from MECP2 conditional deletion.
2018-04-05 | GSE112663 | GEO
Project description:This study investigated mechanisms of peripheral sensory abnormalities in Rett Syndrome using a MeCP2 knockout rat. Dramatic changes in peripheral innervation by DRG sensory neurons were observed in the knockout rats that strongly correlated with modality-specific sensory dysfunction. The cell-autonomous effect of MeCP2 mutation in DRG neurons disrupt axon growth mechanisms leading to the altered cutaneous innervation density. We performed RNA-Seq to compare the transcriptome of MeCP2 KO DRGs with that derived from wildtype littermates. This revealed profound impact of MeCP2 loss on axon growth regulatory pathways in sensory neurons. The findings will have significant impact on our understanding of sensory dysfunctions in Rett syndrome and Autism Spectrum Disorders at large.
2018-02-14 | GSE87855 | GEO
Project description:The goal of this study was to characterize a novel Mecp2 allele in the laboratory rat, a distinct rodent species from the laboratory mouse with unique features. The allele was created by zinc finger-nuclease (ZFN) targeting (SAGE/Horizon) of the X-linked gene, Methyl-CpG-Binding Protein 2 (Mecp2), resulting in normal Mecp2 RNA abundance, but absent protein in male rats as expected due to the presence of only one copy of mutant Mecp2, and an approximate 50% reduction in female rats as expected from animals that harbor one wild-type copy and one mutant copy of Mecp2. Behavioral characterization of female rats with the Mecp2 ZFN allele and wild-type littermates was conducted, and Mecp2 ZFN/+ female rats showed behavioral phenotypes that were consistent with disease-like features present during the early stages of disease onset in the neurological disorder Rett syndrome. The goal of conducting RNAseq studies was to compare existing gene expression alterations in the Mecp2 rat with one of the most widely studied Mecp2 mouse model. Hypothalami were obtained from males with complete loss of MeCP2 (ZFN/y) and wild-type littermate male rats for RNA-seq studies. Common and unique gene expression alterations among the Mecp2 rodents that were then tested in human Rett and control postmortem brain revealed the benefit of combining findings from both models, suggesting the predictive validity of this approach for future studies for the identification of potential preclinical outcome measures. QPCR validation in an independent set of rats was conducted with a subset of genes from the Mecp2 ZFN rat RNA-seq data as an additional control measure. Taken together, these findings demonstrate that the Mecp2 rat model is a complementary tool with unique features for the study of RTT and highlight the potential benefit of cross-species analyses in identifying potential disease-relevant preclinical outcome measures. Transcriptional profiles of hypothalamic samples obtained from male rats haboring a novel zinc-finger nuclease Mecp2 loss-of-function allele and corresponding wild-type littermate rats were generated using RNA-seq
2016-08-09 | E-GEOD-83323 | biostudies-arrayexpress
Project description:We measured the proteome of wild type and Mecp2 KO rat cerebral cortex, hippocampus and cerebrospinal fluid of animals aged 25 days postnatal age. We measured the proteome of human cerebrospinal fluid from Rett syndrome patients before and after treatment with recombinant IGF-1. We measured the proteome of wild type and Mecp2 KO as well as disease associated Mecp2 point mutations in LUHMEs dopaminergic postmitotic neurons. Project details can be found in doi: https://doi.org/10.1101/2021.11.30.470580
2022-10-14 | PXD030426 | Pride
Project description:Rett syndrome (RTT) is a neurodevelopmental disorder characterized by developmental regression around 6-18 months after birth, followed by a lifetime of intellectual disability, stereotyped behaviors, and motor deficits. RTT is caused by mutations in MeCP2, a methyl-CpG binding protein that was traditionally believed to repress gene expression. Gene expression studies of individual brain regions, however, have revealed that MeCP2 loss-of-function leads to the subtle activation and repression of its gene targets. However, these results may be confounded by the extensive neuronal cell heterogeneity inherent in these brain structures. To minimalize this issue of heterogeneity, we assessed whether Mecp2-null mice exhibited alterations in gene expression patterns in the striatum, a brain nucleus with relatively homogenous neuronal types and is highly relevant to the motor deficits observed in RTT. Despite the homogeneity of the tissue, the fold-change of the 127 differentially expressed genes we identified remained low with a mean change consistent with other studies. However, many of those genes differentially expressed in the striatum have not been previously identified in gene expression analyses of other brain regions. This suggests therefore that the differential expression of genes following loss of MeCP2 occurs in a tissue, or cell-type specific manner and thus MeCP2 function should be understood in a cellular context.
2013-07-13 | GSE42895 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE24285: Genome-wide Analysis Reveals Mecp2-dependent Regulation of MicroRNAs in a Mouse Model of Rett Syndrome (mm8 chromosomal tiling arrays) GSE24286: Genome-wide Analysis Reveals Mecp2-dependent Regulation of MicroRNAs in a Mouse Model of Rett Syndrome (mm8 promoter tiling arrays) GSE24320: Genome-wide Analysis Reveals Mecp2-dependent Regulation of MicroRNAs in a Mouse Model of Rett Syndrome (high-throughput small RNA sequencing) Refer to individual Series
2010-09-29 | E-GEOD-24329 | biostudies-arrayexpress
Project description:Human methyl-CpG-binding protein 2 (MeCP2) disruption causes Rett syndrome, an autistic disease prevalent in females. Previous microarray expression profiling studies using tissue homogenate samples from mouse model of the Rett syndrome revealed only modest changes in expression caused by the loss of Mecp2, making it difficult to identify etiology of the Rett syndrome. Here, we carried out cell type specific genome wide expression profiling of Mecp2 null mice in three neuronal cell types. We found a hot spot of Mecp2 affected genes in chromosome 11B3 syntenic to human chromosome 17p13 which has known associations to mental retardation. We also found Mecp2 affected genes are almost non-overlapping between cell types. Cell-adhesion category of genes, however, are commonly overrepresented, suggesting a possible etiology of Rett syndrome Keywords: cell type comparison, disease state analysis, genetic modification Transgenic mice lines which label subpopulations of neurons (G42: fast spiking Parvarbumin positive interneurons, YFPH: layer 5 thick tufted pyramidal neurons, TH: tyrosine hydroxylase positive locus coeruleus neurons) were used to obtain cell type specific expression profiles on Affymetrix microarrays. Females which carry Mecp2 null alleles (and one of the fluorescent alleles) were crossed with males (which may or may not carry one of the fluorescent alleles depending on whether the female has one or not). Male offsprings at around age P40 which carry fluorescent allele and Mecp2 null allele were used for experiments. Littermate males which carry fluorescent allele but not Mecp2 null allele were used for controls. 3 or 4 biological replicates were done for each condition.
2011-11-01 | E-GEOD-8720 | biostudies-arrayexpress
Project description:The goal of this study was to characterize a novel Mecp2 allele in the laboratory rat, a distinct rodent species from the laboratory mouse with unique features. The allele was created by zinc finger-nuclease (ZFN) targeting (SAGE/Horizon) of the X-linked gene, Methyl-CpG-Binding Protein 2 (Mecp2), resulting in normal Mecp2 RNA abundance, but absent protein in male rats as expected due to the presence of only one copy of mutant Mecp2, and an approximate 50% reduction in female rats as expected from animals that harbor one wild-type copy and one mutant copy of Mecp2. Behavioral characterization of female rats with the Mecp2 ZFN allele and wild-type littermates was conducted, and Mecp2 ZFN/+ female rats showed behavioral phenotypes that were consistent with disease-like features present during the early stages of disease onset in the neurological disorder Rett syndrome. The goal of conducting RNAseq studies was to compare existing gene expression alterations in the Mecp2 rat with one of the most widely studied Mecp2 mouse model. Hypothalami were obtained from males with complete loss of MeCP2 (ZFN/y) and wild-type littermate male rats for RNA-seq studies. Common and unique gene expression alterations among the Mecp2 rodents that were then tested in human Rett and control postmortem brain revealed the benefit of combining findings from both models, suggesting the predictive validity of this approach for future studies for the identification of potential preclinical outcome measures. QPCR validation in an independent set of rats was conducted with a subset of genes from the Mecp2 ZFN rat RNA-seq data as an additional control measure. Taken together, these findings demonstrate that the Mecp2 rat model is a complementary tool with unique features for the study of RTT and highlight the potential benefit of cross-species analyses in identifying potential disease-relevant preclinical outcome measures.
2016-08-09 | GSE83323 | GEO
Project description:Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism. MECP2 encodes a methyl-DNA-binding protein that is proposed to function as a transcriptional repressor, but, despite numerous studies examining neuronal gene expression in MeCP2 mutants, no coherent model has emerged for how MeCP2 regulates transcription. Here we identify a genome-wide length-dependent increase in the expression of long genes in neurons lacking MeCP2. This gene misregulation occurs in human RTT brains and correlates with onset and severity of phenotypes in Mecp2 mutant mice, suggesting that the disruption of long gene expression contributes to RTT pathology. We present evidence that MeCP2 represses long genes by binding to brain-enriched, methylated CA dinucleotides within genes and show that loss of methylated CA in the brain recapitulates gene expression defects observed in MeCP2 mutants. We find that long genes encode proteins with neuronal functions, and overlap substantially with genes that have been implicated in autism and Fragile X syndrome. Reversing the overexpression of long genes in neurons lacking MeCP2 can improve some RTT-associated cellular deficits. These findings suggest that a function of MeCP2 in the mammalian brain is to temper the expression of genes in a length-dependent manner, and that mutations in MeCP2 and possibly other autism genes may cause neurological dysfunction by disrupting the expression of long genes in the brain. MeCP2 ChIP-seq from the forebrain and cerebellum of wild-type mice.
2015-03-12 | E-GEOD-60071 | biostudies-arrayexpress