Hippocampal expression data from WT, KO, R270X, and G273X mice at 4 and 9 weeks
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Peng Yu
PROVIDER: E-GEOD-42987 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The postnatal neurodevelopmental disorder Rett syndrome (RTT) is caused by mutations in the gene encoding Methyl-CpG-binding Protein 2 (MeCP2). Despite decades of research, it remains unclear how MeCP2 actually regulates transcription or why RTT features appear only 6-18 months after birth. We examined MeCP2 binding to methylated cytosine in the CH context (mCH, where H = A, C, or T) in the adult mouse brain and found that MeCP2 binds these mCH sites, influencing nucleosome positioning and transcription. Strikingly, this pattern is unique to the mature nervous system, as it requires the increase in mCH after birth to reveal differences in MeCP2 binding to mCG, mCH, and non-methylated DNA elements. This study provides insight into the molecular mechanism governing MeCP2 targeting and how this targeting might contribute to the delayed onset of RTT symptoms. mRNA-Seq were conducted from 7-week-old hypothalamus from MeCP2 knockout mice and their age and genetic background matched wild types control mice. Additonal mRNA-Seq were conducted from 7-week-old hypothalamus from MeCP2 transgenic mice and their age and genetic background matched wild types control mice.
2015-04-15 | E-GEOD-66870 | biostudies-arrayexpress
Project description:The postnatal neurodevelopmental disorder Rett syndrome (RTT) is caused by mutations in the gene encoding Methyl-CpG-binding Protein 2 (MeCP2). Despite decades of research, it remains unclear how MeCP2 actually regulates transcription or why RTT features appear only 6-18 months after birth. We examined MeCP2 binding to methylated cytosine in the CH context (mCH, where H = A, C, or T) in the adult mouse brain and found that MeCP2 binds these mCH sites, influencing nucleosome positioning and transcription. Strikingly, this pattern is unique to the mature nervous system, as it requires the increase in mCH after birth to reveal differences in MeCP2 binding to mCG, mCH, and non-methylated DNA elements. This study provides insight into the molecular mechanism governing MeCP2 targeting and how this targeting might contribute to the delayed onset of RTT symptoms. Mnase-Seq were conducted from 7-week-old hypothalamus from MeCP2 knockout mice and their age and genetic background matched wild types control mice.
2015-04-15 | E-GEOD-66869 | biostudies-arrayexpress
Project description:Hearts of Myh6-MeCP2 transgenic mice and wildtype littermates were rapidly dissected and flash frozen. We used Affymetrix microarrays to assess gene expression changes induced by overexpression of MeCP2 under the control of a cardiomycyte specific promoter. Hearts were dissected 2-3 weeks after birth from transgenic Myh6-MeCP2 mice and littermates to study gene expression alterations.
2015-12-22 | E-GEOD-52797 | biostudies-arrayexpress
Project description:A group of postnatal neurodevelopmental disorders collectively referred to as MeCP2 disorders are caused by aberrations in the gene encoding methyl-CpG-binding protein 2 (MECP2). Loss of MeCP2 function causes Rett syndrome (RTT), whereas increased MeCP2 dosage causes MECP2 duplication or triplication syndromes. MeCP2 acts as a transcriptional repressor, however, the gene expression changes observed in the hypothalamus and cerebellum of MeCP2 disorder mouse models suggest that MeCP2 can also upregulate gene expression. In this study, we compared gene expression changes in the amygdalae of mice lacking MeCP2 (Mecp2-null) and mice overexpressing MeCP2 (MECP2-TG). We chose the amygdala because it is a neuroanatomical region implicated in the control of anxiety and social behavior, two prominent phenotypes in MECP2-TG mice, and hypothesized that transcriptional profiling of this particular brain region may reveal expression changes relevant to heightened anxiety-like behavior and abnormal social behavior. A total of 1,060 genes were altered in opposite directions in both MeCP2 mouse models compared with wild-type littermates, with ~60% up-regulated and ~40% down-regulated. Interestingly, we found a significant enrichment of anxiety- and/or social behavior-related genes among the differentially expressed genes. To determine whether these genes contribute to the anxiety and social behavior phenotypes in MECP2-TG mice, we performed genetic and pharmacologic studies and found that a reduction in Crh suppresses anxiety-like behavior, and a reduction in Oprm1 improves social approach behavior. These studies suggest that MeCP2 impacts molecular pathways involved in anxiety and social behavior, and provide insight into potential therapies for MeCP2 disorders. This study is published in Nature Genetics http://dx.doi.org/10.1038/ng.1066. Total amygdala RNA samples were collected from Mecp2-null male mice (n=4), MECP2-transgenic male mice (n=5), and their wild type male littermates at 6 weeks of age (n=4, n=5 for each group respectively).
2012-01-08 | E-GEOD-33457 | biostudies-arrayexpress
Project description:In utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in adulthood. Pregnant mice were exposed to arsenic, and gene expression patterns were profiled in peripheral lung tissue obtained from the offspring at 2 weeks of age. Pregnant Mice (BALB/c, C57BL/6, C3H/HeARC) mice were exposed to arsenic (or control) via drinking water from day 8 of gestation until the birth of their offspring. After giving birth, mothers were given control drinking water. At 2 weeks post-natal age, total RNA was extracted from peripheral lung tissue of the offspring and analysed on Affymetrix microarrays.
2013-06-04 | E-GEOD-37831 | 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:RTT represents the first genetic cause of severe intellectual disability in girls and although potentially treatable, no cure is currently available. The identification of a valid therapy is delayed by the need of maintaining physiological MeCP2 levels and by the limited comprehension of its roles. Neural precursor cell (NPC) transplantation has already been proved safe and efficacious in many neurological disorders. Particularly, in neurodegenerative conditions, their mechanism of action mainly relies on cell replacement; however, when neurodegeneration is absent, it has been demonstrated that NPCs act by a so-called “bystander” mechanism, by releasing of a plethora of molecules, including inflammatory cytokines, chemokines, trophic factors and stem cell regulators. These factors exert immunomodulatory and neuroprotective effects, and can also modulate synaptic plasticity. Willing to come with a novel cure for RTT, starting from our data indicating the therapeutic potential of NPCs in Mecp2 deficient animals and neurons, we aim at identifying the molecules and/or pathways involved in their therapeutic benefit, a required step for moving the therapy from the bench to the bedside. By bulk RNA sequencing (RNA-seq), we analyzed the transcriptional profile of the hippocampus derived from WT and Mecp2 KO animals, injected with NPCs or vehicle (PBS) at post-natal day (P) 45. Analysis was conducted 20 days after transplantation (at P60). n=5-6 animals/exp.group.
2024-08-27 | E-MTAB-14403 | biostudies-arrayexpress
Project description:RTT represents the first genetic cause of severe intellectual disability in girls and although potentially treatable, no cure is currently available. The identification of a valid therapy is delayed by the need of maintaining physiological MeCP2 levels and by the limited comprehension of its roles. Neural precursor cell (NPC) transplantation has already been proved safe and efficacious in many neurological disorders. Particularly, in neurodegenerative conditions, their mechanism of action mainly relies on cell replacement; however, when neurodegeneration is absent, it has been demonstrated that NPCs act by a so-called “bystander” mechanism, by releasing of a plethora of molecules, including inflammatory cytokines, chemokines, trophic factors and stem cell regulators. These factors exert immunomodulatory and neuroprotective effects, and can also modulate synaptic plasticity. Willing to come with a novel cure for RTT, starting from our data indicating the therapeutic potential of NPCs in Mecp2 deficient animals and neurons, we aim at identifying the molecules and/or pathways involved in their therapeutic benefit, a required step for moving the therapy from the bench to the bedside. By bulk RNA sequencing (RNA-seq), we analyzed the transcriptional profile of the cerebellum derived from WT and Mecp2 KO animals, injected with NPCs or vehicle (PBS) at post-natal day (P) 45. Analysis was conducted 20 days after transplantation (at P60). n=5-6 animals/exp.group.
2024-08-28 | E-MTAB-12813 | 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:Mecp2 loss-of-function has been associated with altered gene expression in many tissues. We characterized gene expression changes within the hippocampi of 3 different Mecp2 loss-of-function mouse models. These studies were used to identify transcriptional differences between these mutants when the mice are largely asymptomatic (4 weeks of age) or have developed overt phenotypes (9 weeks).
2013-03-22 | GSE42987 | GEO