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GSE16438
Mus musculus
23 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A deletion in the CMAH gene in humans occurred approximately 3.5 million years ago. This resulted in the inactivation of the CMP-Neu5Ac hydroxylase enzyme, and hence, in the specific deficiency in N-glycolylneuraminic acid (Neu5Gc), a form of sialic acid, in all modern humans. Although there is evidence that this molecular milestone in the origin of humans may have led to the evolution of human-specific pathogens, how deficiency in Neu5Gc might alter progression of non-infectious human diseases remains unanswered. Here, we have investigated cardiac and skeletal muscle gene expression changes in mdx mice, a model of Duchenne muscular dystrophy (DMD), that do or do not carry the human-like inactivating mutation in the mouse Cmah gene. We have evidence that Neu5Gc-deficiency in humans might explain some of the discrepancies in the disease phenotype between mdx mice and DMD patients.
Publication Title
A human-specific deletion in mouse Cmah increases disease severity in the mdx model of Duchenne muscular dystrophy.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transgenic overexpression of Galgt2 in the skeletal muscles of mdx mice inhibits the development of disease pathology associated with muscular dystrophy. This is the case both in transgenic mice, where Galgt2 overexpression occurs from embryonic timepoints onward and in mdx mice where Galgt2 is overexpressed in the early postnatal period using Adeno-associated virus (AAV). Here, we use gene expression profiling to compare transcriptional changes resulting from embryonic and postnatal Galgt2 overexpression in mdx skeletal muscle. A surprising number of changes were in genes known to ameliorate muscular dystrophy when overexpressed (agrin, integrin alpha 7, ADAM12, Bcl2) or to cause muscular dystrophy when mutated (collagen VI (alpha1,alpha2), plectin 1, dystroglycan, selenoprotein N1, integrin alpha7, biglycan, dysferlin). Several genes involved in calcium homeostasis were also changed. In Galgt2 transgenic mice, where embryonic overexpression of Galgt2 in skeletal muscles alters neuromuscular development and muscle growth, the number of gene expression changes was vastly greater, however, 14% of genes altered in postnatal AAV-Galgt2 infected mdx muscles were also changed with embryonic overexpression. These experiments suggest that postnatal overexpression of Galgt2 inhibits muscular dystrophy in mdx mice via induction of a group of genes that, in aggregate, can govern membrane stability, membrane repair, calcium homeostasis, and apoptosis.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent studies in our lab have identified a mutant mouse model of obstructive nephropathy designated mgb for megabladder. Homozygotic mgb mice (mgb-/-) develop lower urinary tract obstruction in utero due to a lack of bladder smooth muscle differentiation. This defect is the result of a random transgene insertion into chromosome 16 followed by a translocation of this fragment into chromosome 11. In an effort to identify potential gene targets affected in mgb mice, we performed transcriptional profiling on embryonic day 15 (E15) mgb-/- bladders using both a Chromosome 11/16 Custom GeneChip Array and the Affymetrix Mouse Genome 430 2.0 GeneChip. This analysis identified no definitive mis-expressed gene targets on chromosome 11. In contrast, mgb-/- mice significantly over-expressed a cluster of gene products located on the translocated fragment of chromosome 16 including urotensin II-related peptide (Urp), which was shown to be preferentially over-expressed in developing mgb-/- bladders. Immunohistochemical studies indicated that the spatial distribution of Urp was altered in mgb-/- bladders, while biochemical studies suggested a potential role for Urp in modifying smooth muscle cell phenotype in vitro. Pathway analysis of mgb microarray data showed dysregulation of at least 60 gene products associated with the differentiation of smooth muscle. In conclusion, the results of this study indicate that the molecular pathways controlling normal smooth muscle development are severely altered in mgb-/- bladders, and provide the first evidence that Urp may play a critical role in bladder smooth muscle development.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 69 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have identified the molecular (transcriptional) signatures associated with muscle remodeling in response to rehabilitation in a patient cohort. Subjects with a closed malleolus fracture treated conservatively with 6 weeks of cast immobilization are recruited. Then subjects are enrolled in a 6 weeks structured rehabilitation program focusing on progressive resistance training of the ankle plantar flexor muscles. Phenotypic measurements are performed before (pre-rehab), during (mid-rehab, 3 weeks) and immediately after (post-rehab, 6 weeks) the rehabilitation intervention. The maximal cross-sectional area (muscle size) and peak torque (muscle strength) are quantified using isometric and isokinetic tests in combination with 3D-magnetic resonance imaging. Ankle plantar flexor muscle size and strength measurements are also performed on the uninvolved limb (serves as a control) at 4 months post-immobilization. Measurements are also acquired from the contralateral leg, which serves as an internal control.
Publication Title
Molecular signatures of differential responses to exercise trainings during rehabilitation.
Sample Metadata Fields
Sex, Time
View Samples- Rattus norvegicus
- 36 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Spinal cord injury (SCI) is one of the most disabling health problems facing adults today. Locomotor training has been shown to induce substantial recovery in muscle size and muscle function in both transected and contusion injury animal models of SCI.
Publication Title
Transcriptional Pathways Associated with Skeletal Muscle Changes after Spinal Cord Injury and Treadmill Locomotor Training.
Sample Metadata Fields
Time
View Samples- Sus scrofa
- 24 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Background: Skeletal muscle wasting and impaired muscle function in response to mechanical ventilation and immobilization in intensive care unit (ICU) patients are clinically challenging partly due to (i) the poorly understood intricate cellular and molecular networks; and (ii) the unavailability of an animal model mimicking this condition. By employing a unique porcine model mimicking the conditions in the ICU with long-term mechanical ventilation and immobilization, we have analyzed the expression profile of skeletal muscle biopsies taken at three time points during a five-day period.
Publication Title
Gene expression and muscle fiber function in a porcine ICU model.
Sample Metadata Fields
Disease, Time
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background :To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx) from untreated children with juvenile dermatomyositis (JDM) and identify genes and biological processes associated with the disease progression, expression profiling data from 16 girls with active symptoms of JDM greater or equal to 2 months were compared with 3 girls with active symptoms less than 2 months.
Publication Title
Duration of chronic inflammation alters gene expression in muscle from untreated girls with juvenile dermatomyositis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Although short-term disuse does not result in measurable muscle atrophy, studies suggest that molecular changes associated with protein degradation may be initiated within days of the onset of a disuse stimulus. We examined the global gene expression patterns in sedentary men (n = 7, mean age S.D = 22.1 3.7 yr) following 48h unloading (UL) via unilateral lower limb suspension and 24h reloading (RL). Biopsy samples of the left vastus lateralis muscle were collected at baseline, 48h UL, and 24h RL. Expression changes were measured by microarray and gene clustering; identification of enriched functions and canonical pathways were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). Four genes were validated with qRT-PCR, and protein levels were measured with Western blot. Of the upregulated genes after UL, the most enriched functional group and highest ranked canonical pathway were related to protein ubiquitination. The oxidative stress response pathway was the second highest ranked canonical pathway. Of the downregulated genes, functions related to mitochondrial metabolism were the mostly highly enriched. In general, gene expression patterns following UL persisted following RL. qRT-PCR confirmed increases in mRNA for UPP-related E3 ligase Atrogin1 (but not accompanying increases in protein products) and stress response gene heme oxygenase-1 (HMOX, which showed a trend towards increases in protein products at 48h UL) as well as extracellular matrix (ECM) component COL4.
Publication Title
Forty-eight hours of unloading and 24 h of reloading lead to changes in global gene expression patterns related to ubiquitination and oxidative stress in humans.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Following spinal cord injury, skeletal muscle loss is rapid. This severe atrophy is attributed to declines in protein synthesis and increases in protein breakdown. However, the signaling mechanisms controlling these changes are not well understood. Nine male patients and one female patient with spinal cord injury (SCI) (Mean SEM = 43.9 6.7 yrs) were recruited for this study. Six patients were quadriplegics and four patients were paraplegics. Inclusion criteria were as follows: patients above the age of 18 yrs, absence of severe brain injury (Glasgow Coma Scale > 13), absence of muscle-crush injury or compartment syndrome, absence of all of the following conditions: hypoxic injury, systemic sepsis, systemic inflammatory or autoimmune disease, and malignancy. Muscle biopsies were obtained from the vastus lateralis muscles of the SCI patients two days and five days post-SCI. Biopsies collected two days post-SCI were included in the current analysis. Expression changes were measured by microarray and gene clustering; identification of enriched functions and canonical pathways were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA).
Publication Title
Forty-eight hours of unloading and 24 h of reloading lead to changes in global gene expression patterns related to ubiquitination and oxidative stress in humans.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptomic changes induced by DUX4 expression were compared between human and mouse cell lines of muscle lineage.
Publication Title
DUX4 differentially regulates transcriptomes of human rhabdomyosarcoma and mouse C2C12 cells.
Sample Metadata Fields
Specimen part
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