Long non-coding RNAs expression study of a Rett syndrome mouse model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Antonio GM-CM-3mez
PROVIDER: E-GEOD-43689 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:In order to identify some lncRNA potentially involved in Rett syndrome we performed a mouse lncRNA expression microarray on whole brain samples coming from wild-type and MeCP2 Knock-out littermates. We found 2 lncRNAs directly bound by MeCP2 and upregulated in KO samples. We then focused on AK081227 because it overlaps with Gabrr2. The expression of this GABA receptor and the overlapping AK081227 are inversely correlated in thalamus, suggesting the long non-coding is regulating his own host.
2013-10-03 | GSE43689 | 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: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:The thalamus of the brain acts as a relay station; taking inputs from several parts of the brain and then sending the information to the cortex and vice versa. It is also the structure know to affected in several brain developmental disorders such as schizophrenia, autism spectrum disorders, bipolar disorders etc. Upon in situ hybridisation one can visualise the expression of the transcription factor Tcf7l2 to be highest in prosomeric regions of the thalamus throughout development. With this information in mind we set out to find out, if the expression of Tcf7l2 is essential for the identity of the thalamic structure. Therefore, Tcf7l2 was knocked (KO) out using Cre+mice at embryonic stage E18.5 and postnatal adult stage P60. The E18.5 Tcf7l2 KO is a total knockout and the P60 Tcf7l2 KO is neuron-specific knockout. Total RNA was extracted and sent for sequencing using Illumina 2500. The data obtained was aligned by HISAT2 alignment tool, and the excon read counts were gathered using htseq counts, and expression normalization and differential gene expression was analysed using DESeq2.
2020-02-10 | E-MTAB-8755 | biostudies-arrayexpress
Project description:Rett syndrome is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MECP2), an epigenetic regulator of mRNA transcription. Here we report a test of the hypothesis of shared pathophysiology of Rett syndrome and fragile X, another monogenic cause of autism and intellectual disability. In fragile X, the loss of the mRNA translational repressor FMRP leads to exaggerated protein synthesis downstream of metabotropic glutamate receptor 5 (mGluR5). We found that mGluR5- and protein synthesis-dependent synaptic plasticity is similarly altered in area CA1 of Mecp2 KO mice. CA1 pyramidal cell-type-specific, genome-wide profiling of ribosome-bound mRNAs was performed in wild-type and Mecp2 KO hippocampal CA1 neurons to reveal the MeCP2-regulated ‘translatome’. We found significant overlap between ribosome-bound transcripts overexpressed in the Mecp2 KO and FMRP mRNA targets. These tended to encode long genes that are functionally related to either cytoskeleton organization or the development of neuronal connectivity. In the Fmr1 KO mouse, chronic treatment with mGluR5 negative allosteric modulators (NAMs) has been shown to ameliorate many mutant phenotypes by correcting excessive protein synthesis. In the Mecp2 KO mice we found that mGluR5 NAM treatment significantly reduces the level of overexpressed ribosome-associated transcripts, particularly those that are also FMRP targets. Some Rett phenotypes were also ameliorated by treatment, most notably hippocampal cell size and life span. Together, these results suggest a potential mechanistic link between MeCP2-mediated transcription regulation and mGluR5/FMRP-mediated protein translation regulation through co-regulation of a subset of genes relevant to synaptic functions.
2016-12-31 | GSE82068 | GEO
Project description:Analysis of thalamus and hypothalamus under conditions of visual deprivation by dark-rearing (DR). Animals subjected to DR from birth till postnatal day (P) 14. Results provide insight into the role of visual inputs in the regulation of gene expression in thalamus and hypothalamus during development. RNA sample was taken from thalamus and hypothalamus of 14-day-old mouse reared in standard or dark condition. Comparisons among groups were made by one-color method with normalized data from Cy3 channels for data analysis.
2014-01-26 | E-GEOD-53136 | 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. 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: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:MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as post-transcriptional regulators of gene expression. Many miRNAs are expressed in the developing brain and regulate multiple aspects of neural development including neurogenesis, dendritogenesis and synapse formation. Rett syndrome (RTT) is a progressive neurodevelopmental disorder caused by mutations in the gene encoding Methyl-CpG binding protein 2 (MECP2). While Mecp2 is known to act as a global transcriptional regulator, miRNAs that are directly regulated by Mecp2 in the brain are not known. Using massively parallel sequencing methods, we have identified miRNAs whose expression is altered in cerebella of Mecp2-null mice before and after the onset of severe neurological symptoms. In vivo genome-wide analyses indicate that promoter regions of a significant fraction of dys-regulated miRNA transcripts, including a large polycistronic cluster of brain-specific miRNAs, are DNA methylated and directly bound by Mecp2. Functional analysis demonstrates that the 3’ untranslated region (UTR) of messenger RNA encoding Brain-derived neurotrophic factor (Bdnf) can be targeted by multiple miRNAs aberrantly up-regulated in absence of Mecp2. Taken together, these results suggest that dys-regulation of miRNAs may contribute to RTT pathoetiology, and also provide a valuable resource to further investigate the role of miRNAs in RTT. Two pooled total RNA samples (4 pairs of wild-type (WT) and Mecp2-null (KO) male mice; postnatal 6-week, the pre-/early-symptomatic stage) were sequenced in a multiplexed configuration (with distinct barcode sequences). And, six samples (two litters, one WT and two KO male mice in each litter; postnatal 8-week, the symptomatic stage) were sequenced individually.
2010-09-29 | E-GEOD-24320 | biostudies-arrayexpress
Project description:To identify the detailed molecular causes of the mitochondrial dysfunction, oxidative burden and more vulnerable redox balance in Rett mouse hippocampus, we screened for differential gene expression in the hippocampal CA1 subfield of adult male mice. A whole mouse genome microarray was performed to assess, whether key enzymes of the mitochondrial respiratory chain or major cellular radical scavenging enzymes are affected in this MeCP2-deficient mouse model of Rett syndrome. Comparison of gene expression between male wildtype mice (Mecp2+/y) and mice lacking the MECP2 gene (Mecp2-/y) [B6.129P2(C)-Mecp2tm-1-1Bird (Guy et al. 2001, Nat. Genet. 27: 322-326)]. In total, 9 mice of each genotype were analyzed. The mRNA of groups of 3 animals was pooled to generate 3 independent biological samples, and finally three microarrays were run for each genotype.
2012-08-31 | E-GEOD-32870 | biostudies-arrayexpress