E-MTAB-8838
Ontology highlight
ABSTRACT:
TISSUE(S): Cerebellum, Spinal Cord, Cerebral Cortex
PROVIDER: E-MTAB-8838 | ExpressionAtlas | 2021-03-22
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-MTAB-8838-analysis-methods.tsv | Tabular | |||
| E-MTAB-8838-analytics.tsv | Tabular | |||
| E-MTAB-8838-apply_fixes_zooma_mappings.done | Other | |||
| E-MTAB-8838-atlasExperimentSummary.Rdata | Rdata | |||
| E-MTAB-8838-configuration.xml | Xml |
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Project description:Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by motor neuron degeneration. MATR3 is an ALS-linked gene that encodes an RNA-binding protein that is involved in alternative splicing regulation. S85C is the most commonly identified mutation in MATR3. We generated MATR3 S85C knock-in mice (of the C57BL/6 background) as a model to study ALS pathogenesis and we found that homozygous S85C mice begin to show phenotypes at around 10 weeks of age. To investigate the molecular changes that may contribute to the behavioural deficits and neurodegeneration observed in homozygous S85C mice, we performed RNA-seq on cortex, cerebellum and lumbar spinal cord tissue of wild-type, heterozygous and homozygous S85C mice (4 females per genotype) at the early symptomatic stage (8-10 weeks old). Total RNA was extracted and sent to SickKids TCAG core for mRNA library preparation, which were paired end (100 bp in length) sequenced on the Illumina NovaSeq S1 flow cell. The data obtained was aligned to mouse genome (mm10) using STAR aligner (v2.6.0), and paired-end reads mapping to exonic regions were counted using featureCounts (v1.6.3). Differential gene expression was analyzed using edgeR.
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Project description:We have investigated the process of disease-induced functional perturbation and the related transcriptional changes occurring in thoraco-lumbar spinal cord extracted from Sprague-Dawley rats heterozygous for the G93A SOD1 gene mutation (Emerging Model 2148 Het Male, Taconic USA; Wyeth and Amyotrophic Lateral Sclerosis Association 2002) using spinal cord from wild type females littermates as reference tissues. Rats were obtained from a breeding project at Taconic Breeding Services (USA). We have applied large-scale gene expression analysis to define the pattern or transcriptional changes occurring in spinal cord from the G93A SOD1 rat model from a pre-symptomatic stage, at disease onset and at end-stage disease, using Bead Array analysis (Illumina, San Diego, USA). We have pooled spinal cord from N:5 transgenic rats for each of the time points considered, using the same pools of spinal cord from sex and age-matched WT rats as reference. In this specific project, the aim was to obtain a gene ontology (GO) pathway analysis of the transcriptional changes induced by the G93A SOD1 mutation in rat spinal cord. Hence, we have opted for a sample pooling strategy, well aware that in so doing, we would not obtaineed information about individuals genes variation across the samples in study but an overall view of the activation of multi-genes molecular signals.
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