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GSE21795
Homo sapiens
6 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Myotonic dystrophes (DM), the most common adult muscular dystrophy, are the first recognized examples of RNA-mediated diseases in which expression of mutant RNAs containing expanded CUG or CCUG repeats interfere with the splicing of other mRNAs. Using whole-genome microarrays, we found that alternative splicing of the BIN1 mRNA is altered in DM skeletal muscle tissues, resulting in the expression of an inactive form of BIN1 deprived of phosphoinositide-binding and membrane-tubulating activities. BIN1 is involved in tubular invaginations of the plasma membrane and is essential for biogenesis of the muscle T-tubules, which are specialized skeletal muscle membrane structures essential to correct excitation-contraction (E-C) coupling. Mutations in the BIN1 gene cause centronuclear myopathy (CNM) that shares some histopathological features with DM, and both diseases are characterized by muscle weakness. Consistent with a loss-of-function of BIN1, muscle T-tubules were altered in DM patients, and membrane tubulation was restored upon expression of the correct splicing form of BIN1 in DM muscle cells. By deciphering the mechanism of BIN1 splicing mis-regulation we demonstrate that the splicing regulator, MBNL1, which is sequestered by expanded CUG and CCUG in DM, binds the BIN1 pre-mRNA and regulates directly its alternative splicing. Finally, reproducing BIN1 splicing alteration in mice is sufficient to reproduce the DM features of T-tubule alterations and muscle weakness. We propose that alteration of BIN1 alternative splicing regulation leads to muscle weakness, a predominant pathological feature of DM.
Publication Title
Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured biomarker inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1-/-), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75 or 0.85 mg/kg/d CPO from gestational days (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), RBC acylpeptide hydrolase (APH), plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1-/- and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1-/- mice, but not in other genotypes.
Publication Title
Repeated gestational exposure of mice to chlorpyrifos oxon is associated with paraoxonase 1 (PON1) modulated effects in maternal and fetal tissues.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Chlorpyrifos (CPF) is an organophosphorus (OP) insecticide that is still widely used despite statutory restrictions on home use. CPF is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver. Paraoxonase (PON1) polymorphisms affects the catalytic efficiency of the hydrolysis of OPs, including CPO. We used both wt (PON1+/+) and PON1 knockout (PON1-/-) mice and PON1-/- mice carrying transgenes encoding the human alloforms tgHuPON1Q192 and tgHuPON1R192 to gain insight into the mechanisms of neurotoxicity of CPO throughout postnatal development, and to ascertain the importance of the PON1Q192R polymorphism for protecting against developmental toxicity of CPO. Whole-genome microarrays were used to measure gene expression changes associated with chronic CPO exposure of developing (PND 4-21) PON1-/-, tgHuPON1Q192R transgenic and PON1+/+ mice.
Publication Title
Repeated developmental exposure of mice to chlorpyrifos oxon is associated with paraoxonase 1 (PON1)-modulated effects on cerebellar gene expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 59 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We identified fibro-inflammatory and keratin gene expression signatures in systemic sclerosis skin.
Publication Title
Dissecting the heterogeneity of skin gene expression patterns in systemic sclerosis.
Sample Metadata Fields
Age, Specimen part, Race, Subject, Time
View Samples- Homo sapiens
- 59 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We identified eighty two skin transcripts significantly correlated with the severity of interstitial lung disease (ILD) in systemic sclerosis.
Publication Title
Skin gene expression correlates of severity of interstitial lung disease in systemic sclerosis.
Sample Metadata Fields
Age, Specimen part, Race, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Microgravity as well as chronic muscle disuse are two causes of low back pain originated at least in part from paraspinal muscle deconditioning. At present no study investigated the complexity of the molecular changes in human or mouse paraspinal muscles exposed to microgravity. The aim of this study was to evaluate longissimus dorsi and tongue (as a new potential in-flight negative control) adaptation to microgravity at global gene expression level. C57BL/N6 male mice were flown aboard the BION-M1 biosatellite for 30 days (BF) or housed in a replicate flight habitat on ground (BG). . Global gene expression analysis identified 89 transcripts differentially regulated in longissimus dorsi of BF vs. BG mice (False Discovery Rrate < 0,05 and fold change < -2 and > +2), while only a small number of genes were found differentially regulated in tongue muscle ( BF vs. BG = 27 genes).
Publication Title
Microgravity-Induced Transcriptome Adaptation in Mouse Paraspinal <i>longissimus dorsi</i> Muscle Highlights Insulin Resistance-Linked Genes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Microgravity exposure as well as chronic muscle disuse are two of the main causes of physiological adaptive skeletal muscle atrophy in humans and murine animals in physiological condition. The aim of this study was to investigate, at both morphological and global gene expression level, skeletal muscle adaptation to microgravity in mouse soleus and extensor digitorum longus (EDL). Adult male mice C57BL/N6 were flown aboard the BION-M1 biosatellite for 30 days on orbit (BF) or housed in a replicate flight habitat on Earth (BG) as reference flight control.
Publication Title
Gene Expression Profiling in Slow-Type Calf Soleus Muscle of 30 Days Space-Flown Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
CNS-delivery of Interleukin 4 (IL-4) - via a lentiviral-mediated gene therapy strategy - skews microglia to proliferate, inducing these cells to adopt the phenotype of slowly proliferating cells. Transcriptome analysis revealed that IL-4-treated microglia express a broad number of genes normally encoded by embryonic microglia. Overall design: RNAseq analysis of sorted microglia from mice receiving IL-4 gene therapy
Publication Title
Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Analysis of alternative splicing in heart (left ventricles) samples of 3 adult DM1 patients versus 3 adult controls Overall design: PolyA RNA from left ventricles (heart) of 3 controls and 3 DM1 patients were analysed by massive parrallel sequencing
Publication Title
Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Analysis of alternative splicing of left ventricles heart samples of 3 DM1 adult versus 3 adult controls
Publication Title
Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples