Mice cerbellum extracts: SCA7 KI mice vs. wild type mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE49115 | GEO | 2013/07/24
SECONDARY ACCESSION(S): PRJNA213047
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptional profiling of mouse cerebellar extract comparing SCA7 KI mice with wild type mice. Female mice were killed by decapitation on post natal days 10 and 22 and 11 weeks. Goal was to determine gene expression profiles differing between SCA7 KI mice and wild-type mice during post-natal developement of the cerebellum. Gene expression profiling was performed using RNA extracted from the cerebellum of KI and WT mice at P10 (5 WT and 5 KI), P22 (5 WT and 4 KI) and 11 wks (5WT and 6 KI). After labeling, RNAs were hybridized on dual-label G4122F AgilentM-BM-. chips; a mix of all P10 samples was used as common reference (green channel). Quality control included visual control of the reconstructed image of the chip, M/A plot, corner intensities, outliers, positive and negative intensities, normalization factors. Normalization and statistical analyses were carried out by using BRB-array Tools developed by Dr. Richard Simon and the BRB-ArrayTools development team (Biometrics Research Branch, http://linus.nci.nih.gov/BRB-ArrayTools.html). Genes with less than 50% present calls or with low variability along the arrays (less than 20% of values with at least 2-fold change in either direction from the geneM-bM-^@M-^Ys median value) were excluded from further analysis. For the 1905 remaining probes an interaction between time and genotype was analyzed by regression analysis of the time course of expression. In brief, probes for which variation over time differed for the genotype class were fitted to the following model: log expression ~ time + time**2 + genotype + genotype*time + genotype*time**2. A univiariate p-value < 0.001 (random variance model) was set for significant probes (genotype*time + genotype*time**2) and a False Discovery Rate (FDR) was calculated for each probe (Benjamini & Hochberg, 1995). Differences in profiles were identified with a Self Organisation Tree Algorithm (MultiplExperiment Viewer (MeV), (Saeed et al, 2006). Expression values were averaged by group and then clustered according to their profile as a function of time.
2013-07-24 | E-GEOD-49115 | biostudies-arrayexpress
Project description:To determine if STAGA complex dysfunction affects chromatin remodeling in SCA7 cerebellar degeneration, we pursued unbiased ChIP-Seq analysis of histone 3 lysine 9 acetylation (H3K9ac), as this histone mark is an established indicator of open chromatin in the transcription regulatory regions of most genes. We studied SCA7 266Q knock-in mice which faithfully recapitulate a severe, rapidly progressive neurodegenerative phenotype involving the cerebellum. We detected altered H3K9ac in the promoter regions of 777 genes in the cerebellum of SCA7 266Q knock-in mice and wild-type littermate control mice, and noted that the vast majority of these chromatin alterations corresponded to markedly increased H3K9 promoter acetylation in genes expressed in the cerebellum of SCA7 model mice.
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Project description:To assess differently expressed genes beween wt and ki fibroblasts Total RNA was purified from fibroblasts of 3 different mice for wt and 3 different mice for ki
2016-06-01 | E-GEOD-80825 | biostudies-arrayexpress
Project description:Age-associated Changes in the Transcriptome of SCA7 Mice
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Project description:Antigen Ki-67 is a nuclear protein expressed in proliferating mammalian cells. It is widely used in cancer histopathology but its functions remain unclear. Here, we show that Ki-67 controls heterochromatin organisation. Altering Ki-67 expression levels did not significantly affect cell proliferation in vivo. Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently. Conversely, upregulation of Ki-67 expression in differentiated tissues did not inhibit cell cycle arrest. Ki-67 interactors included proteins involved in nucleolar processes and chromatin regulators. Ki-67 depletion disrupted nucleologenesis but did not inhibit pre-rRNA processing. In contrast, it altered gene expression. Ki-67 silencing also had wide-ranging effects on chromatin organisation, disrupting heterochromatin compaction and long-range genomic interactions. Trimethylation of histone H3K9 and H4K20 at heterochromatin was strongly reduced. Overexpression of human or Xenopus Ki-67 induced ectopic heterochromatin formation. Altogether, our results suggest that Ki-67 expression in proliferating cells spatially organises heterochromatin, thereby controlling gene expression.
2018-10-26 | PXD003551 | Pride
Project description:Mice cerbellum extracts: SCA7 KI mice vs. wild type mice
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Project description:Microglial dysfunction is a key pathological feature of Alzheimer´s disease (AD), but little is known about proteome-wide changes in microglia during the course of AD pathogenesis and their consequences for microglial function. Here, we performed an in-depth proteomic characterization of microglia in two AD mouse models, the overexpression APPPS1 and the knock-in AppNL-G-F (APP-KI) model. Proteome changes were followed from pre-deposition to early, middle and advanced stages of amyloid plaque pathology, revealing a large panel of Microglial Amyloid Response Proteins (MARPs) that reflect a heterogeneity of microglial alterations triggered by Adeposition. We demonstrate that the occurrence of MARPs coincided with the deposition of fibrillar A, recruitment of microglia to amyloid plaques and phagocytic dysfunction. While the proteomic and functional microglial changes were already markedly seen in 3 months old APPPS1 mice, they were delayed in the APP-KI model that generates substantially less fibrillar A. The identified microglial proteomic fingerprints of AD provide a valuable resource for functional studies of novel molecular targets and potential biomarkers for monitoring AD progression or therapeutic efficacy.
2020-06-09 | PXD016075 | Pride
Project description:Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease mainly characterized by motor incoordination due to progressive cerebellar degeneration. SCA7 is caused by polyglutamine expansion in ATXN7, a subunit of the transcriptional coactivator SAGA, which harbors histone modification activities. Polyglutamine expansions in specific proteins are also responsible for SCA1-3, 6 and 17, however, the converging and diverging pathomechanisms remain poorly understood. Using a new SCA7 knock-in mouse, SCA7140Q/5Q, we analyzed gene expression in the cerebellum and assigned gene deregulation to specific cell types using published datasets. Gene deregulation affects all cerebellar cell types, although at variable degree, and correlates with alterations of SAGA-dependent epigenetic marks. Purkinje cells (PCs) are by far the most affected neurons and show reduced expression of 83 cell-type identity genes, including these critical for their spontaneous firing activity and synaptic functions. PC gene downregulation precedes morphological alterations, pacemaker dysfunction and motor incoordination. Strikingly, most PC genes downregulated in SCA7 have also decreased expression in SCA1 and SCA2 mice, revealing converging pathomechanisms and a common disease signature involving cGMP-PKG and phosphatidylinositol signaling pathways and long-term depression. Our study thus points out molecular targets for therapeutic development, which may prove beneficial for several SCAs. Furthermore, we show that SCA7140Q/5Q males and females exhibit the major disease features observed in patients, including cerebellar damage, cerebral atrophy, peripheral nerves pathology and photoreceptor dystrophy, which account for progressive impairment of behavior, motor and visual functions. SCA7140Q/5Q mice represent an accurate model for the investigation of different aspects of SCA7.
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