Gene expression profiling of muscles from transgenic humanSODG93A mice at presymptomatic stage
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Manuela Volta
PROVIDER: E-GEOD-16360 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The transgenic mice expressing the human mutated form (G93A) of the SOD1 gene represent a valuable model of Amyotrophic Lateral Sclerosis (ALS). SOD1 is one of the main causative genes of familial ALS which accounts for 10% of cases. These transgenic animals develop a motorneuronal pathology that recapitulates well the neuropatological features occuring in ALS patients, and the progression of the disease can be monitored by a series of motor tests. Gastrocnemius is first and most affected muscle in the disease, while triceps is relatively spared. Gene expression data of degenerating motor neurons at different disease stages are already available, while gene expression data on the muscle tissue are missing. Our aim is to define the role of muscle in motor neuron degeneration in ALS. Keywords: Single stage analysis (early symptomatic stage, 14 weeks-old mice) We considered two sets of muscle at symptomatic stage (14 weeks): gastrocnemius and triceps from 4 transgenic SOD1G93A and 4 non-transgenic mice (NTg). Gastrocnemius from 4 nerve-crushed mice were also considered as controls for the denervation process
2010-03-04 | E-GEOD-16361 | biostudies-arrayexpress
Project description:The transgenic mice expressing the human mutated form (G93A) of the SOD1 gene represent a valuable model of Amyotrophic Lateral Sclerosis (ALS). SOD1 is one of the main causative genes of familial ALS which accounts for 10% of cases. These transgenic animals develop a motorneuronal pathology that recapitulates well the neuropathological features occuring in ALS patients, and the progression of the disease can be monitored by a series of motor tests. Gastrocnemius is the first and most affected muscle in the disease, while triceps is relatively spared. Gene expression data of degenerating motor neurons at different disease stages are already available, while gene expression data on the muscle tissue are missing. Our aim is to define the role of muscle in motor neuron degeneration in ALS. Keywords: Single stage analysis (presymptomatic stage, 7 week-old mice)
2009-06-02 | GSE16360 | GEO
Project description:The transgenic mice expressing the human mutated form (G93A) of the SOD1 gene represent a valuable model of Amyotrophic Lateral Sclerosis (ALS). SOD1 is one of the main causative genes of familial ALS which accounts for 10% of cases. These transgenic animals develop a motorneuronal pathology that recapitulates well the neuropatological features occuring in ALS patients, and the progression of the disease can be monitored by a series of motor tests. Gastrocnemius is first and most affected muscle in the disease, while triceps is relatively spared. Gene expression data of degenerating motor neurons at different disease stages are already available, while gene expression data on the muscle tissue are missing. Our aim is to define the role of muscle in motor neuron degeneration in ALS. Keywords: Single stage analysis (early symptomatic stage, 14 weeks-old mice)
2009-06-02 | GSE16361 | GEO
Project description:Recent genetic studies of ALS patients have identified several forms of ALS that are associated with mutations in RNA binding proteins. In animals or cultured cells, such defects broadly affect RNA metabolism. This raises the question of whether all forms of ALS have general effects on RNA metabolism. We tested this hypothesis in a mouse model of ALS that is transgenic for a human disease-causing mutation in the enzyme superoxide dismutase 1 (SOD1). We analyzed RNA from laser-captured spinal cord motor neuron cell bodies of the mutant SOD1 strain, comparing the RNA profile with that from a corresponding wild-type SOD1 transgenic strain. We prepared the samples from animals that were presymptomatic, but which manifested abnormalities at the cellular level that are seen in ALS, including aggregation of the mutant protein in motor neuron cell bodies and defective morphology of neuromuscular junctions, the connections between neuron and muscle. We observed only minor changes in the level and splicing of RNA in the SOD1 mutant animals as compared with wild-type, suggesting that mutant SOD1 produces the toxic effects of ALS by a mechanism that does not involve global RNA disturbance. RNA-Seq of laser microdissection of motor neuron bodies from two biological replicates each of SOD1 YFP (wildtype 592) and SOD1 G85R YFP (737) transgenic mice.
2012-12-04 | E-GEOD-38820 | biostudies-arrayexpress
Project description:Recent genetic studies of ALS patients have identified several forms of ALS that are associated with mutations in RNA binding proteins. In animals or cultured cells, such defects broadly affect RNA metabolism. This raises the question of whether all forms of ALS have general effects on RNA metabolism. We tested this hypothesis in a mouse model of ALS that is transgenic for a human disease-causing mutation in the enzyme superoxide dismutase 1 (SOD1). We analyzed RNA from laser-captured spinal cord motor neuron cell bodies of the mutant SOD1 strain, comparing the RNA profile with that from a corresponding wild-type SOD1 transgenic strain. We prepared the samples from animals that were presymptomatic, but which manifested abnormalities at the cellular level that are seen in ALS, including aggregation of the mutant protein in motor neuron cell bodies and defective morphology of neuromuscular junctions, the connections between neuron and muscle. We observed only minor changes in the level and splicing of RNA in the SOD1 mutant animals as compared with wild-type, suggesting that mutant SOD1 produces the toxic effects of ALS by a mechanism that does not involve global RNA disturbance.
2012-12-04 | GSE38820 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease that affects motoneurons. Mutations in superoxide dismutase 1 (SOD1) have been described as a causative genetic factor for ALS. Mice overexpressing ALS-linked mutant SOD1 develop ALS symptoms accompanied by histopathological alterations and protein aggregation. Protein disulfide isomerase family member ERp57 is one of the main up-regulated proteins in tissue of ALS patients and mutant SOD1 mice, whereas point mutations in ERp57 were described as possible risk factors. ERp57 catalyzes disulfide bond formation and isomerization in the endoplasmic reticulum (ER), constituting a central component of protein quality control mechanisms. However, the actual contribution of ERp57 to ALS pathogenesis remains to be defined. Here, we studied the consequences of overexpressing ERp57 in ALS onset and progression of mutant SOD1G93A mice. The double transgenic SOD1G93A/ERp57WT mice presented improved motor performance, in addition to delayed deterioration of electrophysiological activity of affected muscles compared to single transgenic SOD1G93A littermates at early symptomatic stage. The overexpression of ERp57 reduced mutant SOD1 aggregation, but only at disease end-stage. Instead, the neuroprotective effects of ERp57 were correlated with preserved muscle innervation. Importantly, proteomic analysis revealed that the overexpression of ERp57 increases the levels of synaptic proteins in the spinal cord. Taken together, our results suggest that ERp57 operates as a disease modifier at early stages by maintaining motoneuron connectivity.
2021-02-08 | PXD023647 | Pride
Project description:Familial amyotrophic lateral sclerosis (ALS) represents about 10% of ALS cases. In about 20% of familial ALS patients, a mutation in superoxide dismutase-1 (SOD1) can be found. The ubiquitous SOD1 protein converts superoxide radical anions to oxygen and hydrogen peroxide. Patients with familial ALS caused by mutations in SOD1 can show comorbidity with frontotemporal dementia and develop cognitive impairment, including apathy, inattention, verbal deficits, and hypersexuality. At the cellular level, pathological signs of ALS may include tau immunoreactive astrocytic and neuronal inclusions, suggesting that cognitive dysfunction in ALS may also reflect abnormal protein metabolism of the microtubule associated protein (MAP), tau. To identify cell-specific expression changes, we performed laser capture microdissection (LCM) to isolate anterior horn motor neurons and surrounding cells. To determine common pathways for the development of ALS due to dysfunction of SOD1 or TAU, we performed whole transcriptome analysis in SOD1 and TAU mouse models. Because ALS is a neurodegenerative disease that specifically affects motor neurons, these cells were the main investigative target. Global transcriptomes of glial cells surrounding the motor neurons were also assessed, because these cells have been implicated as triggers of neurodegeneration. Mouse experiments were performed at the presymptomatic stage, prior to the onset of cell loss, in order to reduce false positive signals due to tissue reactive changes. Lumbar anterior horn anterior horn motor neurons and surrounding cells (glia) were isolated from presymptomatic TAU-P301L and SOD1-G93A transgenic mice using laser capture microdissection (LCM; PixCell® IIe LCM System, Arcturus, Molecular Devices, CA). On average, 500 motor neuron bodies or surrounding glial cells from 20 tissue sections per animal were collected. RNA isolation from LCM collected cells was performed using the Qiagen RNeasy Micro Kit. Only RNA with RNA Integrity Numbers (RIN) above 7.5 were taken for further analysis (Agilent Bioanalyzer 2100). A two-round T7-based amplification and labeling protocol (Agilent Low RNA Input Linear Amplification Kit PLUS) was used to generate high quality labeled cRNA. Agilent Whole Mouse Genome Microarray comparisons of motor neurons and surrounding glia were performed between transgenic (SOD1G93A and TAUP301L) and corresponding nontransgenic (control) littermate animals, producing four independent comparison groups: SOD1G93A motor neurons versus control motor neurons (SOD1mn), SOD1G93A motor neuron surrounding glia versus control glia (SOD1gl), TAUP301L motor neurons versus control motor neurons (TAUmn) and TAUP301L glia versus control glia (TAUgl). Each comparison used four pairs of transgenic (SOD1G93A or TAUP301L) vs. corresponding control littermate animals, producing four biological replicates. Raw microarray data were acquired using the Agilent DNA Microarray scanner and processed with the accompanying Agilent Feature Extraction 10.5 Image Analysis software using default settings. Normalized signal intensities were used to identify gene expression changes in SOD1G93A and TAUP301L motor neurons and surrounding glial cells, generating four partially overlapping sets of data. For the identification of differential expression, the genes were required to pass two conservative criteria: a ratio beyond the 99.5% confidence interval observed in homotypic comparisons, which corresponded to an approximately 1.5-fold expression change, and a paired t-test (P<0.01) computed using 100 permutations of the data for each gene. Correction for multiple comparisons was performed using the adjusted Bonferroni test. The analysis was performed in the TM4: Microarray Software Suite. These techniques identified 251 transcripts representing 186 known genes for which expression was altered in at least one of the four comparisons. Four-condition experiment, SOD1G93A motor neurons versus control motor neurons (SODmn), SOD1G93A motor neuron surrounding glia versus control glia (SODgl), TAUP301L motor neurons versus control motor neurons (TAUmn) and TAUP301L glia versus control glia (TAUgl). Each comparison used four pairs of transgenic (SOD1G93A or TAUP301L) vs. corresponding control littermate animals, producing four biological replicates. Biological replicates: 4 SOD1G93A motor neurons (SODmn), 4 non SOD littermate motor neurons (nonSODmn), 4 SOD1G93A motor neuron surrounding glia (SODgl), 4 non SOD littermate motor neuron surrounding glia (nonSODgl), 4 TAUP301L motor neurons (TAUmn), 4 non TAU littermate motor neurons (nonTAUmn), 4 TAUP301L motor neuron surrounding glia (TAUgl), 4 non TAU littermate motor neuron surrounding glia (nonTAUgl). Four independent comparison groups were generated: SOD1G93A motor neurons versus control nonSOD motor neurons, SOD1G93A motor neuron surrounding glia versus control nonSOD glia, TAUP301L motor neurons versus control nonTAU motor neurons and TAUP301L glia versus control nonTAU glia. Each comparison used four pairs of transgenic (SOD1G93A or TAUP301L) vs. corresponding control littermate animals, producing four biological replicates. Each replicate was repeated twice with dye flip to correct for unequal dye incorporation rates. Therefore, eight microarray hybridizations were performed for each biological comparison, for a total of 32 microarray slides and generating four groups of differentially expressed genes in SOD1G93A motor neurons (SODmn), SOD1G93A motor neuron surrounding glial cells (SODgl), TAUP301L motor neurons (TAUmn), and TAUP301L surrounding glial cells (TAUgl).
2010-07-30 | E-GEOD-22482 | biostudies-arrayexpress
Project description:Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neuromuscular disorder characterized by the selective degeneration of upper and lower motor neurons, progressive muscle wasting and paralysis. To define the full set of alterations in gene expression in skeletal muscle during the course of the disease, we performed high-density oligonucleotide microarray analysis of gene expression in hind limb skeletal muscles of sod1(G86R) mice, one of the existing transgenic models of ALS. To monitor denervation-dependent gene expression, we determined the effects of short-term acute denervation on the muscle transcriptome after sciatic nerve axotomy.
2008-01-05 | E-TABM-195 | biostudies-arrayexpress
Project description:Familial amyotrophic lateral sclerosis (ALS) represents about 10% of ALS cases. In about 20% of familial ALS patients, a mutation in superoxide dismutase-1 (SOD1) can be found. The ubiquitous SOD1 protein converts superoxide radical anions to oxygen and hydrogen peroxide. Patients with familial ALS caused by mutations in SOD1 can show comorbidity with frontotemporal dementia and develop cognitive impairment, including apathy, inattention, verbal deficits, and hypersexuality. At the cellular level, pathological signs of ALS may include tau immunoreactive astrocytic and neuronal inclusions, suggesting that cognitive dysfunction in ALS may also reflect abnormal protein metabolism of the microtubule associated protein (MAP), tau. To identify cell-specific expression changes, we performed laser capture microdissection (LCM) to isolate anterior horn motor neurons and surrounding cells. To determine common pathways for the development of ALS due to dysfunction of SOD1 or TAU, we performed whole transcriptome analysis in SOD1 and TAU mouse models. Because ALS is a neurodegenerative disease that specifically affects motor neurons, these cells were the main investigative target. Global transcriptomes of glial cells surrounding the motor neurons were also assessed, because these cells have been implicated as triggers of neurodegeneration. Mouse experiments were performed at the presymptomatic stage, prior to the onset of cell loss, in order to reduce false positive signals due to tissue reactive changes. Lumbar anterior horn anterior horn motor neurons and surrounding cells (glia) were isolated from presymptomatic TAU-P301L and SOD1-G93A transgenic mice using laser capture microdissection (LCM; PixCell® IIe LCM System, Arcturus, Molecular Devices, CA). On average, 500 motor neuron bodies or surrounding glial cells from 20 tissue sections per animal were collected. RNA isolation from LCM collected cells was performed using the Qiagen RNeasy Micro Kit. Only RNA with RNA Integrity Numbers (RIN) above 7.5 were taken for further analysis (Agilent Bioanalyzer 2100). A two-round T7-based amplification and labeling protocol (Agilent Low RNA Input Linear Amplification Kit PLUS) was used to generate high quality labeled cRNA. Agilent Whole Mouse Genome Microarray comparisons of motor neurons and surrounding glia were performed between transgenic (SOD1G93A and TAUP301L) and corresponding nontransgenic (control) littermate animals, producing four independent comparison groups: SOD1G93A motor neurons versus control motor neurons (SOD1mn), SOD1G93A motor neuron surrounding glia versus control glia (SOD1gl), TAUP301L motor neurons versus control motor neurons (TAUmn) and TAUP301L glia versus control glia (TAUgl). Each comparison used four pairs of transgenic (SOD1G93A or TAUP301L) vs. corresponding control littermate animals, producing four biological replicates. Raw microarray data were acquired using the Agilent DNA Microarray scanner and processed with the accompanying Agilent Feature Extraction 10.5 Image Analysis software using default settings. Normalized signal intensities were used to identify gene expression changes in SOD1G93A and TAUP301L motor neurons and surrounding glial cells, generating four partially overlapping sets of data. For the identification of differential expression, the genes were required to pass two conservative criteria: a ratio beyond the 99.5% confidence interval observed in homotypic comparisons, which corresponded to an approximately 1.5-fold expression change, and a paired t-test (P<0.01) computed using 100 permutations of the data for each gene. Correction for multiple comparisons was performed using the adjusted Bonferroni test. The analysis was performed in the TM4: Microarray Software Suite. These techniques identified 251 transcripts representing 186 known genes for which expression was altered in at least one of the four comparisons.
2010-06-24 | GSE22482 | GEO
Project description:In familial forms of amyotrophic lateral sclerosis (ALS) caused by mutations in superoxide dismutase-1 (SOD1) gene, both cell-autonomous and non-cell-autonomous mechanisms lead to the selective degeneration of motoneurons. Gene-targeted deletion of mutated SOD1 in mature astrocytes has been shown to slow down disease progression. However, the potential therapeutic application of targeting astrocytes has not been evaluated yet. Here, an AAV vector encoding an artificial microRNA is used to deliver RNA interference against mutated SOD1 by targeting astrocytes in ALS mice. In mice expressing the mutated SOD1G93A protein, we found that the treatment leads to the progressive rescue of neuromuscular junction occupancy, to the recovery of the compound muscle action potential in the gastrocnemius muscle, and significantly improves neuromuscular function. In the spinal cord, gene therapy targeting astrocytes protects a small pool of fast-fatigable motoneurons until disease end stage. In the gastrocnemius muscle of the treated SOD1G93A mice, the fast-twitch type IIb muscle fibers are preserved from atrophy. Axon collateral sprouting is observed together with muscle fiber type grouping indicative of denervation/re-innervation events. The transcriptome profiling of spinal cord motoneurons shows changes in the expression levels of factors regulating the dynamics of microtubules. Gene therapy delivering RNA interference against mutated SOD1 in astrocytes provides therapeutic effects enhancing motoneuron plasticity and improving neuromuscular function in ALS mice.
2022-01-31 | GSE148901 | GEO