In this paper we constructed a simple mathematical model to investigate the role of the immune response in muscle degeneration and subsequent regeneration in the mdx mouse model of Duchenne muscular dystrophy. (hindawi.com)
Background: Duchenne muscular dystrophy is a progressive, lethal muscle-wasting disease for which there is no treatment. (illinois.edu)
Materials & methods: We have isolated wild-type mesoangioblasts from aorta and tested their effectiveness in alleviating severe muscle disease in the dystrophin/utrophin knockout (mdx/utrn -l- ) mouse model for Duchenne muscular dystrophy. (illinois.edu)
To facilitate gene and cell therapy experiments, we created severely immune-deficient mouse models of Duchenne muscular dystrophy (DMD), limb girdle muscular dystrophy 2B (LGMD2B), and limb girdle muscular dystrophy 2D (LGMD2D) by crossing mdx 4Cv , Bl/AJ, and Sgca-null mice with NRG immune-deficient mice. (plos.org)
Dystrophin8
This mutation in the murine dystrophin gene caused an absence of dystrophin in skeletal muscle and this key defect validated the mdx mouse as a suitable model of the early onset of DMD human disease [ 5 , 6 ]. (hindawi.com)
Repeated peptide-AO treatments resulted in high levels of cardiac dystrophin protein, which prevented the exercised induced progression of cardiomyopathy, normalising heart size as well as stabilising other cardiac parameters. (ox.ac.uk)
This work demonstrates that high levels of cardiac dystrophin restored by Pip peptide-AOs prevents further deterioration of cardiomyopathy and pathology following exercise in dystrophic DMD mice. (ox.ac.uk)
Pip5 transduction peptides direct high efficiency oligonucleotide-mediated dystrophin exon skipping in heart and phenotypic correction in mdx mice. (ox.ac.uk)
Antisense oligonucleotide (AO)-mediated exon skipping has been shown to restore functional dystrophin in mdx mice and DMD patients treated intramuscularly in two recent phase 1 clinical trials. (ox.ac.uk)
How much dystrophin is enough: the physiological consequences of different levels of dystrophin in the mdx mouse. (ox.ac.uk)
These data define the dystrophin restoration levels required to slow down or prevent disease progression and improve overall muscle function once a dystrophic environment has been established in the mdx mouse model. (ox.ac.uk)
Furthermore, the impact upon heterozygous female mdx carriers ( mdx /+), who display dystrophin mosaicism, has received little attention. (frontiersin.org)
Skeletal2
Treatment with BGP-15 similarly increased SERCA activity in dystrophic skeletal muscles. (ox.ac.uk)
Lastly, inhibition of the strong autophagic program observed in adolescent mdx male mice via administration of the autophagy inhibitor leupeptin did not improve skeletal muscle pathology. (frontiersin.org)
C57BL4
identified a spontaneous mutation in C57BL/10ScSn inbred mice that exhibited a disease state similar to human DMD [ 4 ]. (hindawi.com)
Mice, Inbred C57BL" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (uchicago.edu)
This graph shows the total number of publications written about "Mice, Inbred C57BL" by people in this website by year, and whether "Mice, Inbred C57BL" was a major or minor topic of these publications. (uchicago.edu)
Below are the most recent publications written about "Mice, Inbred C57BL" by people in Profiles. (uchicago.edu)
Transgenic1
This strain is commonly used as genetic background for transgenic mouse models. (uchicago.edu)
Dystrophy2
The X chromosome-linked mutation resulted in mice ( mdx mice) with high serum levels of muscle enzymes and with histological lesions comparable to those seen in human muscular dystrophy. (hindawi.com)
Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. (ox.ac.uk)
Phenotype2
To determine their therapeutic value, dystrophic mdx mice were subject to forced exercise to model the DMD cardiac phenotype. (ox.ac.uk)
By contrast, the phenotype of the BlAJ/NRG mice was milder in each case. (plos.org)
Oligonucleotides1
Here, we modelled the treatment of muscle with pre-existing dystrophic pathology using antisense oligonucleotides conjugated to a cell-penetrating peptide. (ox.ac.uk)
Muscles3
Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. (ox.ac.uk)
In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death, BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. (ox.ac.uk)
We found that the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA, the main protein responsible for the removal of intracellular Ca(2+)) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. (ox.ac.uk)
Therapeutic2
Critical to the therapeutic success of AO-based treatment will be the ability to deliver AOs systemically to all affected tissues including the heart. (ox.ac.uk)
Our results provide evidence that increasing the expression of Hsp72 in muscle (through the administration of BGP-15) has significant therapeutic potential for DMD and related conditions, either as a self-contained therapy or as an adjuvant with other potential treatments, including gene, cell and pharmacological therapies. (ox.ac.uk)
Histology2
The histology and time course of the disease in mdx mouse model are very different from those in DMD patients: relatively normal life span and overall fitness compared to progressive physical impairment leading to death in DMD patients [ 7 ]. (hindawi.com)
We performed centronucleation, Evans blue dye, hydroxyproline, and treadmill assays on the disease model mice versus NRG controls to evaluate muscle histology and function. (plos.org)
Therapy3
Currently, there are no effective means of therapy or treatment for DMD. (hindawi.com)
Immunosuppressive therapy, such as treatment with glucocorticoids, improves muscle strength and prolongs ambulation in DMD patients but does not prevent disease progression [ 3 , 12 ]. (hindawi.com)
These novel immune-deficient mouse models of DMD, LGMD2B, and LGMD2D will be useful for long-term gene and cell therapy studies involving transfer of foreign genes and cells. (plos.org)
Model5
During early disease onset, the mdx mouse has been validated as an animal model for DMD and use of this model has led to valuable but incomplete insights into the disease process. (hindawi.com)
Furthermore, the analysis of the model predicts that the immune system response oscillates throughout the life of the mice, and the damaged fibers are never completely cleared. (hindawi.com)
Nonetheless, the mdx mouse model is regarded as the best animal model, especially of the early onset of DMD. (hindawi.com)
The article [ 13 ] is a comprehensive literature review of the immune-mediated molecular and signaling mechanisms that regulate the time course of the disease and the mdx mouse model. (hindawi.com)
Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model. (uchicago.edu)
Genetic2
The genetic defect responsible for DMD has been known for over 25 years, yet at present there is neither cure nor effective treatment for DMD. (hindawi.com)
Because of their monoallelic genetic basis, the addition of genes or cells that could provide the DMD, SGCA, or DYSF protein that is deficient in these disorders has the potential to be an effective treatment. (plos.org)
Male1
In this study, we detected aberrant mitochondrial morphology, reduced cristae number, and large mitochondrial vacuoles from both male and female mdx mice prior to the onset of muscle damage. (frontiersin.org)
Functional1
In order to robustly evaluate functional improvement, we used in situ protocols in the mdx mouse to measure muscle strength and resistance to eccentric contraction-induced damage. (ox.ac.uk)
High1
We further detected mild metabolic and mitochondrial impairments in female mdx carrier mice that were exacerbated with high-fat diet feeding. (frontiersin.org)
Present1
These results are in line with previous data and suggest that before the onset of myofiber necrosis, mitochondrial and metabolic abnormalities are present within the mdx mouse. (frontiersin.org)
Models1
Immunoglobulin G subclasses confer protection against Staphylococcus aureus bloodstream dissemination through distinct mechanisms in mouse models. (uchicago.edu)
Significant1
These studies demonstrated that the mdx 4Cv /NRG and Sgca/NRG mice showed significant deficits in muscle structure and function in all the assays and were similar to each other. (plos.org)
Time1
Effects of Depilatory Cream Formulation and Contact Time on Mouse Skin. (uchicago.edu)
Response1
Gut microbiota modulates bleomycin-induced acute lung injury response in mice. (uchicago.edu)
Muscular Dystrophy3
Therapy-responsive biomarkers are an important and unmet need in the muscular dystrophy field where new treatments are currently in clinical trials. (ox.ac.uk)
The same treatment also enhances regeneration and function of dystrophic muscles in mdx mice, a model for Duchenne muscular dystrophy. (nih.gov)
ADAM12 is a disintegrin and metalloprotease, previously demonstrated to significantly alleviate the pathology of mdx mice, a model for Duchenne muscular dystrophy in humans. (ox.ac.uk)
Transgenic mice2
First, we analyzed transgenic mice that overexpress ADAM12 and found mild myopathic changes and accelerated regeneration following acute injury. (ox.ac.uk)
We then analyzed changes in gene-expression profiles in mdx/ADAM12 transgenic mice compared with their littermate controls and found only a few genes with an expression change greater than 2-fold between mdx/ADAM12 and mdx. (ox.ac.uk)
Dystrophin6
Levels of MYOM3 fragments were assayed in therapeutic model systems: (1) restoration of dystrophin expression by antisense oligonucleotide-mediated exon-skipping in mdx mice and (2) stable restoration of α-sarcoglycan expression in KO-SGCA mice by systemic injection of a viral vector. (ox.ac.uk)
These results suggest that a combination of promoting muscle regenerative capacity and preventing muscle necrosis could be an effective treatment for the secondary symptoms caused by the primary loss of dystrophin. (nih.gov)
Pip5 transduction peptides direct high efficiency oligonucleotide-mediated dystrophin exon skipping in heart and phenotypic correction in mdx mice. (ox.ac.uk)
Antisense oligonucleotide (AO)-mediated exon skipping has been shown to restore functional dystrophin in mdx mice and DMD patients treated intramuscularly in two recent phase 1 clinical trials. (ox.ac.uk)
In the present study we demonstrated that ADAM12 may compensate for the dystrophin deficiency in mdx mice by increasing the expression and redistribution of several components of the muscle cell-adhesion complexes. (ox.ac.uk)
In conclusion, these results demonstrate a novel way to alleviate dystrophin deficiency in mice, and may stimulate the development of new approaches to compensate for dystrophin deficiency in animals and humans. (ox.ac.uk)
Necrosis1
More specifically ADAM12 appeared to prevent muscle cell necrosis in the mdx mice as evidenced by morphological analysis and by the reduced levels of serum creatine kinase. (ox.ac.uk)
Pathology1
The small changes in gene expression were unexpected, considering the marked improvement of the mdx pathology when ADAM12 is overexpressed, and suggested that significant changes in mdx/ADAM12 muscle might occur post-transcriptionally. (ox.ac.uk)
Hypertrophy1
Diaphragms of transgenic mdx:mIgf+/+ exhibited significant hypertrophy and hyperplasia at all ages observed. (nih.gov)
Regeneration1
Because insulin-like growth factor I (IGF-I) has been shown to enhance muscle regeneration and protein synthetic pathways, we asked whether high levels of muscle-specific expression of IGF-I in mdx muscle could preserve muscle function in the diseased state. (nih.gov)
Expression1
Furthermore, the IGF-I expression significantly reduced the amount of fibrosis normally observed in diaphragms from aged mdx mice. (nih.gov)
Animals1
Decreased myonecrosis was also observed in diaphragms and quadriceps from mdx:mIgf+/+ mice when compared with age-matched mdx animals. (nih.gov)
Heart1
Critical to the therapeutic success of AO-based treatment will be the ability to deliver AOs systemically to all affected tissues including the heart. (ox.ac.uk)