Transcriptome profiling of spinal motor atrophy mice skeletal muscle tissue
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA666557 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Spinal motor atrophy mice (SMN delta 7 mice) and wild-type control hindlimb skeletal muscle tissue was used for transcriptome profiling by mRNA-seq.
2021-03-01 | GSE158790 | GEO
Project description:To identify the gene expression changes by administering PG to SBMA model mice, we prepared total RNA samples from the spinal cords and skeletal muscles of transgenic mice carrying a full-length human AR with 97 CAGs (AR-97Q) that were treated with or without PG. We used AR-97Q (Line #7-8) male mice because they show progressive muscular atrophy and weakness as well as SBMA-like pathology such as the accumulation of the pathogenic androgen receptor in the nucleus of motor neurons. Using microarray analysis, we identified the genes with significantly altered expression of AR-97Q mice by PG treatment. For non-treated and PG-treated groups, we examined the male mice at 13 weeks of age. RNA from the total spinal cord and skeletal muscle was isolated from three mice of each group.
2013-10-29 | E-GEOD-51807 | biostudies-arrayexpress
Project description:Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s Disease, is a slowly progressive adult-onset neuromuscular disease which results from a polyglutamine (polyQ) encoding CAG repeat expansion within the androgen receptor gene (AR). Despite the ubiquitous expression of the androgen receptor, it is unclear why motor neurons selectively degenerate and there are no effective treatments or disease modifying therapies for this debilitating disease. In order to identify potential therapeutic targets, we set out to establish the genes and molecular pathways involved in early motor neuron dysfunction in SBMA. We therefore undertook global transcriptomic profiling of cultured primary embryonic motor neurons from the spinal cord of AR100 mice, which model SBMA.. Four biological replicate samples were used for genome wide analysis using Affymetrix 430 v2.0 mouse arrays. Data was normalised using therobust multichip average (RMA) algorithm.
2019-05-02 | E-MTAB-6986 | biostudies-arrayexpress
Project description:Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy
2009-12-07 | E-MEXP-2428 | biostudies-arrayexpress
Project description:The survival motor neuron 1 (SMN1) gene is the causative gene for the spinal muscular atrophy (SMA) disease, the first genetic cause of infant mortality. It affects primarily motor neurons which are the targets of the approved genetic therapies aimed to compensate for the loss of SMN1. However, the limitations of these therapies are now evident since they are not cures, and alternative strategies need to be investigated. Because of the ubiquitous and multifunctional roles of SMN1 in the cell, deeper understanding of the molecular mechanisms underlying intrinsic abnormalities of the different tissues affected by SMA is crucial for the development of new therapeutic approaches. Here we used a muscle specific genetic mouse model for the identification of key cellular processes associated to SMN1 loss, at single myofiber level. We found that mitochondrial dysfunction is a key pathogenetic event in SMA: mitochondria are abnormal with internal degenerated cristae. The ultrastructural changes are coincident with alterations in ROS levels by monoamine oxidase A and Ca2+ homeostasis. Interestingly, the improvements of the myopathic phenotype of the muscle-specific SMA model mice by transplantation of amniotic fluid stem (AFS) cells led to restore mitochondrial function. Our data suggest that a mitochondria-targeting therapy may represent a complementary and broad treatment strategy to further optimize the current treatment.
2023-03-08 | GSE207890 | GEO
Project description:To identify the gene expression changes by administering PG to SBMA model mice, we prepared total RNA samples from the spinal cords and skeletal muscles of transgenic mice carrying a full-length human AR with 97 CAGs (AR-97Q) that were treated with or without PG. We used AR-97Q (Line #7-8) male mice because they show progressive muscular atrophy and weakness as well as SBMA-like pathology such as the accumulation of the pathogenic androgen receptor in the nucleus of motor neurons. Using microarray analysis, we identified the genes with significantly altered expression of AR-97Q mice by PG treatment.
2013-10-29 | GSE51807 | GEO
Project description:Spinal Muscular Atrophy (SMA) is well-known to be caused by mutations in the gene Survival of Motor Neuron 1 (SMN1). Because this gene is ubiquitously expressed, it remains poorly understood why motor neurons (MNs) are one of the most affected cell types. To begin to address this question, we carried out RNA-sequencing studies using fixed, antibody-labeled and purified MNs produced from control and SMA patient-derived induced pluripotent stem cells (iPSCs). We found SMA-specific changes in MNs, including hyper-activation of the endoplasmic reticulum (ER) stress pathway and enhanced apoptosis. Functional studies demonstrated that inhibition of ER stress improves overall MN health and survival in vitro even in MNs with low SMN levels. In SMA mice, we show that systemic delivery of an ER stress inhibitor that crosses the blood-brain-barrier led to preservation of MNs in the spinal cord and prolonged survival of these mice. Therefore, our study implies that selective activation of ER stress underlies MN death in SMA. Moreover, the approach we have taken would be broadly applicable to studying disease-prone human cells in heterogeneous cultures. total RNA collected from ES cell and patient ES cell derived spinal motor neurons
2015-09-01 | E-GEOD-69175 | biostudies-arrayexpress
Project description:Proximal spinal muscular atrophy (SMA) is an early onset, autosomal recessive motor neuron disease caused by loss of or mutation in SMN1 (survival motor neuron 1). Despite understanding the genetic basis underlying this disease, it is still not known why motor neurons (MNs) are selectively affected by the loss of the ubiquitously expressed SMN protein. Using a mouse embryonic stem cell (mESC) model for severe SMA, the RNA transcript profiles (transcriptomes) between control and severe SMA (SMN2+/+;mSmn-/-) mESC-derived MNs were compared in this study using massively parallel RNA sequencing (RNA-Seq). The MN differentiation efficiencies between control and severe SMA mESCs were similar. RNA-Seq analysis identified 3094 upregulated and 6964 downregulated transcripts in SMA mESC-derived MNs when compared against control cells. Pathway and network analysis of the differentially expressed RNA transcripts showed that pluripotency and cell proliferation transcripts were significantly increased in SMA MNs while transcripts related to neuronal development and activity were reduced. The differential expression of selected transcripts such as Crabp1, Crabp2 and Nkx2.2 was validated in a second mESC model for SMA as well as in the spinal cords of low copy SMN2 severe SMA mice. Furthermore, the levels of these selected transcripts were restored in high copy SMN2 rescue mouse spinal cords when compared against low copy SMN2 severe SMA mice. These findings suggest that SMN deficiency affects processes critical for normal development and maintenance of MNs. RNA profiles were generated from FACS-purified control and SMA mESC-derived motor neurons (n=3/genotype) by deep sequencing using Illumina HighSeq 2500
2014-09-08 | E-GEOD-56284 | biostudies-arrayexpress
Project description:Sestrin prevents skeletal muscle atrophy
| PRJNA563889 | ENA
Project description:Motor neurons are selectively vulnerable in spinal muscular atrophy (SMA). However, some brainstem motor neuron groups, including oculomotor and trochlear, which innervate the muscles around the eyes, are for unknown reasons spared. Here, we investigate the transcriptional dynamics in discrete neuronal populations in health and SMA to identify mechanisms of vulnerability and resistance. Such mechanisms could reveal targets for future gene therapy studies aimed towards preserving vulnerable motor neurons.
2020-07-11 | GSE115706 | GEO