Mus musculus
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ABSTRACT:
PROVIDER: PRJNA282741 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The pattern of gene expression changes was analyzed in the skeletal muscle of transgenic mouse models of Spinal and bulbar muscular atrophy (SBMA) at 1 and 2 month of age.
2023-01-19 | GSE221480 | GEO
Project description:Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by a polyglutamine expansion in the androgen receptor (AR). Transcriptional changes were compared between a muscle cell model of SBMA (AR-97Q cells) and a control model (AR-24Q cells). RNA-seq gene expression analysis revealed that differentially expressed genes were associated with upregulation of transforming growth factor β (TGFβ) signaling, mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF) signaling, calcium signaling, and NFκB signaling.
2024-11-05 | GSE252533 | GEO
Project description:The goal of this study was to determine the transcriptomic response of AR-2 (AR45) overexpression in the TA muscles of the AR100Q murine model of SBMA (spinal and bulbar muscular atrophy). Conclusion: AAV-AR45 therapy resulted in a partial restoration of the SBMA-like expression signature compared with mock-treated controls.
2021-06-29 | GSE166655 | GEO
Project description:X-linked Spinal and Bulbar Muscular Atrophy (SBMA) is a rare, late-onset neuromuscular disease caused by a CAG repeat expansion mutation in the androgen receptor (AR) gene. SBMA is characterized by progressive muscle atrophy of both neurogenic and myopathic etiologies. Previous work has established that mutant AR expression in skeletal muscle could be a significant contributor to neuromuscular decline, yet the mechanisms involved remain ill-defined. As AR is a nuclear hormone receptor transcription factor, we sought to define early changes in gene expression in skeletal muscle of pre-symptomatic SBMA mice, with a focus on transcriptional changes at the neuromuscular junction (NMJ). We describe loss of key NMJ-specific genes in synaptic muscle regions of pre-symptomatic SBMA mice, while extrasynaptic muscle features a coordinated loss of sarcomere genes that coincides with ectopic re-expression of certain NMJ genes. Furthermore, SBMA muscle prominently features dysregulated calcium flux, likely stemming from a compensatory response to early atrophy that greatly exacerbates over time. The SERCA activator CDN1163 conferred a mild rescue in function and muscle size in SBMA mice, while genetic deletion of the gene encoding Myf6/MRF4, a negative regulator of sarcomere gene expression and predicted AR interactor, did not ameliorate muscle atrophy. These studies suggest that modulation of calcium flux could be a promising pharmacological target in SBMA.
2025-05-16 | GSE296707 | GEO
Project description:Degeneration of the neuromuscular system is a characteristic feature of spinal and bulbar muscular atrophy (SBMA), a CAG/polyglutamine (polyQ) expansion disorder caused by mutation in the androgen receptor (AR). Using a gene targeted mouse model of SBMA, AR113Q mice, we demonstrate age-dependent degeneration of the neuromuscular system that initially manifests with muscle weakness and atrophy and progresses to include denervation of neuromuscular junctions and lower motor neuron soma atrophy. Using this model, we tested the hypothesis that therapeutic intervention targeting skeletal muscle during this period of disease progression arrests degeneration of the neuromuscular system. To accomplish this, AR-targeted antisense oligonucleotides were administered subcutaneously to symptomatic AR113Q mice to reduce expression of polyQ AR in peripheral tissues but not in the spinal cord. This intervention rescued muscle atrophy, neuromuscular junction innervation, lower motor neuron soma size, and survival in aged AR113Q mice. Single-nucleus RNA sequencing revealed age-dependent transcriptional changes in the AR113Q spinal cord during disease progression which were mitigated by peripheral AR gene silencing. Our findings underscore the intricate interplay between peripheral tissues and the central nervous system in SBMA and emphasize the therapeutic effectiveness of peripheral gene knockdown in symptomatic disease.
2025-08-04 | GSE300077 | GEO
Project description:Degeneration of the neuromuscular system is a characteristic feature of spinal and bulbar muscular atrophy (SBMA), a CAG/polyglutamine (polyQ) expansion disorder caused by mutation in the androgen receptor (AR). Using a gene targeted mouse model of SBMA, AR113Q mice, we demonstrate age-dependent degeneration of the neuromuscular system that initially manifests with muscle weakness and atrophy and progresses to include denervation of neuromuscular junctions and lower motor neuron soma atrophy. Using this model, we tested the hypothesis that therapeutic intervention targeting skeletal muscle during this period of disease progression arrests degeneration of the neuromuscular system. To accomplish this, AR-targeted antisense oligonucleotides were administered subcutaneously to symptomatic AR113Q mice to reduce expression of polyQ AR in peripheral tissues but not in the spinal cord. This intervention rescued muscle atrophy, neuromuscular junction innervation, lower motor neuron soma size, and survival in aged AR113Q mice. Single-nucleus RNA sequencing revealed age-dependent transcriptional changes in the AR113Q spinal cord during disease progression which were mitigated by peripheral AR gene silencing. Our findings underscore the intricate interplay between peripheral tissues and the central nervous system in SBMA and emphasize the therapeutic effectiveness of peripheral gene knockdown in symptomatic disease.
2025-07-31 | GSE264689 | GEO
Project description:Muscle-specific gene expression changes in spinal and bulbar muscular atrophy (SBMA) at presymptomatic timepoint
| PRJNA908776 | ENA
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:RNA sequence was performed using mRNAs of motor neurons derived from iPSCs of four patients of spinal bulbar muscular atrophy (SBMA) and four age- and sex- matched controls. The analysis was performed using purified motor neurons by flowcytometry and cell sorting based on the expression of HB9e438::Venus reporter gene (P4) or unpurified motor neurons (NT).
2020-03-02 | GSE142612 | GEO
Project description:Despite the discovery of many genetic risk factors, the cause of the motor neuron death that drives terminal pathology in Amyotrophic Lateral Sclerosis (ALS) remains unknown. We report that the skeletal muscle of ALS patients secretes exosomal vesicles that are specifically toxic to motor neurons. This could not be attributed to a trivial down-stream consequence of muscle denervation. In a study of muscle biopsies and biopsy-derived denervation-naïve differentiated muscle stem cells (myotubes) from 67 human subjects, including healthy and disease controls, ALS myotubes had a consistent signature of disrupted exosome biogenesis and RNA-processing, and their exosomes induced shortened, less branched, neurites, greater death, and disrupted localization of RNA and RNA-processing proteins in motor neurons. Toxicity was dependent on presence of the FUS protein, which is highly expressed in recipient motor neurons. As part of this work, we carried out gene expression analysis of myotubes (differentiated myoblasts) comparing ALS against two other motor neuron disorders as disease controls (SBMA, Spinal and bulbar muscular atrophy; and Spinal Muscular Atrophy Type 4, SMA-IV) and healthy controls.
2022-04-19 | GSE122261 | GEO