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)
Using this technique the mdx mouse, a model of Duchenne muscular dystrophy (DMD) was examined. (ox.ac.uk)
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)
Phenotype2
By contrast, the phenotype of the BlAJ/NRG mice was milder in each case. (plos.org)
To determine their therapeutic value, dystrophic mdx mice were subject to forced exercise to model the DMD cardiac phenotype. (ox.ac.uk)
C57BL1
identified a spontaneous mutation in C57BL/10ScSn inbred mice that exhibited a disease state similar to human DMD [ 4 ]. (hindawi.com)
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)
Knockout2
To directly assess the role of nNOS in mdz muscle, we generated dystrophin-nNOS double knockout mice by mating nNOS single knockout mice with mdx mice. (johnshopkins.edu)
The double knockout mice are indistinguishable from the rndx mice in terms of dystrophic muscle morphology and sarcolemma membrane damage. (johnshopkins.edu)
Skeletal muscle2
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)
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)
Muscular2
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)
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)
Dystrophin5
Furthermore, the impact upon heterozygous female mdx carriers ( mdx /+), who display dystrophin mosaicism, has received little attention. (frontiersin.org)
Hence, nNOS absence in mdx and DMD tissue is likely a secondary effect to the loss of dystrophin and does not participate in the disease pathogenesis. (johnshopkins.edu)
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)
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)
Necrosis1
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)
Histology2
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)
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)
Model5
In contrast, Noggin was found to be a potent and selective BMP inhibitor and was therefore tested in vivo in a DMD mouse model. (nih.gov)
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)
Cardiac1
Treated mice also exhibited significantly reduced cardiac fibrosis and improved sarcolemmal integrity. (ox.ac.uk)
Tissue1
The progressive pathology of DMD can be explained by an insufficient regenerative response resulting in fibrosis and adipose tissue formation. (nih.gov)
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)
Functional2
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)
A principal problem in understanding the functional genomics of a pathology is the wide-reaching biochemical effects that occur when the expression of a given protein is altered. (ox.ac.uk)
Treatment2
Prevention of exercised induced cardiomyopathy following Pip-PMO treatment in dystrophic mdx mice. (ox.ac.uk)
Here, we modelled the treatment of muscle with pre-existing dystrophic pathology using antisense oligonucleotides conjugated to a cell-penetrating peptide. (ox.ac.uk)
Results1
These results indicate that the mdx pathology does not directly result from aberrant localization of nNOS. (johnshopkins.edu)
Disease1
We tested the hypothesis that misl0calization or misregulation of nNOS in dystrophic muscle contributes to the disease pathology. (johnshopkins.edu)
Models1
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)
Damage1
However, whether mitochondrial dysfunction occurs before muscle fiber damage in DMD pathology is not well known. (frontiersin.org)
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)
Muscular Dystrophy2
Characterization of Alzheimer's disease-like neuropathology in Duchenne's muscular dystrophy using the DBA/2J mdx mouse model. (ox.ac.uk)
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)
Transgenic4
In transgenic mdx mice expressing mIgf-I (mdx:mIgf+/+), we showed that muscle mass increased by at least 40% leading to similar increases in force generation in extensor digitorum longus muscles compared with those from mdx mice. (nih.gov)
Diaphragms of transgenic mdx:mIgf+/+ exhibited significant hypertrophy and hyperplasia at all ages observed. (nih.gov)
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)
Skeletal1
Structural and Functional Alterations of Skeletal Muscle Microvasculature in Dystrophin-Deficient mdx Mice. (ox.ac.uk)
Dystrophin3
To clarify the role of these SP cells in muscle regeneration,we injected green fluorescent protein (GFP)-positive myoblasts with or without CD31(-) CD45(-) SP cells into the tibialis anterior muscles of immunodeficient NOD/scid mice or dystrophin-deficient mdx mice. (elsevierpure.com)
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)
Muscle6
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)
In addition to muscle pathology, some patients with DMD will exhibit cognitive impairments with severity being linked to age and type of genetic mutation. (ox.ac.uk)
For the first time, our study focused on old (12-month-old) mdx mice, displaying marked chronic muscle lesions, similar to the lesions observed in human DMD, in comparison to young-adult (3-month-old) mdx mice displaying only mild muscle lesions with no fibrosis. (ox.ac.uk)
By using an original approach combining a specific animal model, state-of-the-art histology/morphometry techniques, and functional nuclear magnetic resonance, we demonstrated that the microvascular system is almost normal in young-adult in contrast to old mdx mice, displaying marked microvessel alterations, and the functional repercussions on muscle perfusion and bioenergetics after a hypoxic stress vary depending on stage of pathology. (ox.ac.uk)
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)
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)
Fibrosis1
Furthermore, the IGF-I expression significantly reduced the amount of fibrosis normally observed in diaphragms from aged mdx mice. (nih.gov)
Significantly1
Serological analysis showed that anti-myostatin IgG titers were significantly increased, and serum creatine kinase was significantly reduced in the BLS-M22-treated mdx mice compared to the control 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)
Study1
Thus, in this study we examined cognitive function in age-matched C57 and D2 mdx mice along with their respective WT controls. (ox.ac.uk)