Journal articles: 'Muscular dystrophy X-linked mouse (mdx)'

1

Dangain, J., and IR Neering. "Mouse Models of Muscular Dystrophy: Gene Products and Function." Physiology 7, no. 5 (October 1, 1992): 195–99. http://dx.doi.org/10.1152/physiologyonline.1992.7.5.195.

Full text

Abstract:

With the discovery of the X-linked gene product dystrophin, the mdx mouse came to be regarded as the only suitable mouse model of human muscular dystrophy. However, existence of an autosomal gene homologous with dystrophin, together with physiological evidence of membrane fragility, reestablishes autosomal mouse mutants (dy, dy2j) as valid models.

APA, Harvard, Vancouver, ISO, and other styles

2

Carberry, Steven, Margit Zweyer, Dieter Swandulla, and Kay Ohlendieck. "Profiling of Age-Related Changes in theTibialis AnteriorMuscle Proteome of the mdx Mouse Model of Dystrophinopathy." Journal of Biomedicine and Biotechnology 2012 (2012): 1–11. http://dx.doi.org/10.1155/2012/691641.

Full text

Abstract:

X-linked muscular dystrophy is a highly progressive disease of childhood and characterized by primary genetic abnormalities in the dystrophin gene. Senescent mdx specimens were used for a large-scale survey of potential age-related alterations in the dystrophic phenotype, because the established mdx animal model of dystrophinopathy exhibits progressive deterioration of muscle tissue with age. Since the mdxtibialis anteriormuscle is a frequently used model system in muscular dystrophy research, we employed this particular muscle to determine global changes in the dystrophic skeletal muscle proteome. The comparison of mdx mice aged 8 weeks versus 22 months by mass-spectrometry-based proteomics revealed altered expression levels in 8 distinct protein species. Increased levels were shown for carbonic anhydrase, aldolase, and electron transferring flavoprotein, while the expressions of pyruvate kinase, myosin, tropomyosin, and the small heat shock protein Hsp27 were found to be reduced in aged muscle. Immunoblotting confirmed age-dependent changes in the density of key muscle proteins in mdx muscle. Thus, segmental necrosis in mdxtibialis anteriormuscle appears to trigger age-related protein perturbations due to dystrophin deficiency. The identification of novel indicators of progressive muscular dystrophy might be useful for the establishment of a muscle subtype-specific biomarker signature of dystrophinopathy.

APA, Harvard, Vancouver, ISO, and other styles

3

Joseph, Josiane, Dong Cho, and Jason Doles. "Metabolomic Analyses Reveal Extensive Progenitor Cell Deficiencies in a Mouse Model of Duchenne Muscular Dystrophy." Metabolites 8, no. 4 (October 3, 2018): 61. http://dx.doi.org/10.3390/metabo8040061.

Full text

Abstract:

Duchenne muscular dystrophy (DMD) is a musculoskeletal disorder that causes severe morbidity and reduced lifespan. Individuals with DMD have an X-linked mutation that impairs their ability to produce functional dystrophin protein in muscle. No cure exists for this disease and the few therapies that are available do not dramatically delay disease progression. Thus, there is a need to better understand the mechanisms underlying DMD which may ultimately lead to improved treatment options. The muscular dystrophy (MDX) mouse model is frequently used to explore DMD disease traits. Though some studies of metabolism in dystrophic mice exist, few have characterized metabolic profiles of supporting cells in the diseased environment. Using nontargeted metabolomics we characterized metabolic alterations in muscle satellite cells (SCs) and serum of MDX mice. Additionally, live-cell imaging revealed MDX-derived adipose progenitor cell (APC) defects. Finally, metabolomic studies revealed a striking elevation of acylcarnitines in MDX APCs, which we show can inhibit APC proliferation. Together, these studies highlight widespread metabolic alterations in multiple progenitor cell types and serum from MDX mice and implicate dystrophy-associated metabolite imbalances in APCs as a potential contributor to adipose tissue disequilibrium in DMD.

APA, Harvard, Vancouver, ISO, and other styles

4

Lewis, Caroline, Harald Jockusch, and Kay Ohlendieck. "Proteomic Profiling of the Dystrophin-Deficient MDX Heart Reveals Drastically Altered Levels of Key Metabolic and Contractile Proteins." Journal of Biomedicine and Biotechnology 2010 (2010): 1–20. http://dx.doi.org/10.1155/2010/648501.

Full text

Abstract:

Although Duchenne muscular dystrophy is primarily classified as a neuromuscular disease, cardiac complications play an important role in the course of this X-linked inherited disorder. The pathobiochemical steps causing a progressive decline in the dystrophic heart are not well understood. We therefore carried out a fluorescence difference in-gel electrophoretic analysis of 9-month-old dystrophin-deficient versus age-matched normal heart, using the established MDX mouse model of muscular dystrophy-related cardiomyopathy. Out of 2,509 detectable protein spots, 79 2D-spots showed a drastic differential expression pattern, with the concentration of 3 proteins being increased, including nucleoside diphosphate kinase and lamin-A/C, and of 26 protein species being decreased, including ATP synthase, fatty acid binding-protein, isocitrate dehydrogenase, NADH dehydrogenase, porin, peroxiredoxin, adenylate kinase, tropomyosin, actin, and myosin light chains. Hence, the lack of cardiac dystrophin appears to trigger a generally perturbed protein expression pattern in the MDX heart, affecting especially energy metabolism and contractile proteins.

APA, Harvard, Vancouver, ISO, and other styles

5

Wells, Dominic J., Aurora Ferrer, and Kim E. Wells. "Immunological hurdles in the path to gene therapy for Duchenne muscular dystrophy." Expert Reviews in Molecular Medicine 4, no. 23 (November 4, 2002): 1–23. http://dx.doi.org/10.1017/s146239940200515x.

Full text

Abstract:

Patients with Duchenne muscular dystrophy (DMD), an X-linked lethal muscle-wasting disease, have abnormal expression of the protein dystrophin within their muscle fibres. In the mdx mouse model of this condition, both germline and neonatal somatic gene transfers of dystrophin cDNAs have demonstrated the potential of gene therapy in treating DMD. However, in many DMD patients, there appears to be no dystrophin expression when muscle biopsies are immunostained or western blots are performed. This raises the possibility that the expression of dystrophin following gene transfer might trigger a destructive immune response against this ‘neoantigen’. Immune responses can also be generated against the gene transfer vector used to transfect the dystrophic muscle, and the combined immune response could further damage the already inflamed muscle. These problems are now beginning to be investigated in immunocompetent mdx mice. Although much work remains to be done, there are promising indications that these immune responses might not prove as much of a concern as originally envisaged.

APA, Harvard, Vancouver, ISO, and other styles

6

Tanabe, Y., K. Esaki, and T. Nomura. "Skeletal muscle pathology in X chromosome-linked muscular dystrophy (mdx) mouse." Acta Neuropathologica 69, no. 1-2 (1986): 91–95. http://dx.doi.org/10.1007/bf00687043.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

Kurihara, Teruyuki, Masahiko Kishi, Nobuyuki Saito, Michiji Komoto, Takanobu Hidaka, and Masao Kinoshita. "Electrical myotonia and cataract in X-linked muscular dystrophy (mdx) mouse." Journal of the Neurological Sciences 99, no. 1 (October 1990): 83–92. http://dx.doi.org/10.1016/0022-510x(90)90202-x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Petrof, B. J., H. H. Stedman, J. B. Shrager, J. Eby, H. L. Sweeney, and A. M. Kelly. "Adaptations in myosin heavy chain expression and contractile function in dystrophic mouse diaphragm." American Journal of Physiology-Cell Physiology 265, no. 3 (September 1, 1993): C834—C841. http://dx.doi.org/10.1152/ajpcell.1993.265.3.c834.

Full text

Abstract:

The X chromosome-linked muscular dystrophic (mdx) mouse lacks the subsarcolemmal protein dystrophin and thus represents a genetic homologue of human Duchenne muscular dystrophy. The present study examined alterations in diaphragm contractile properties and myosin heavy chain (MHC) expression in young (3-4 mo) and old (22-24 mo) control and mdx mice. In young mdx mice, maximum isometric tension (Po) was reduced to 50% of control values. An increase in fibers coexpressing types I (slow) and IIa MHC as well as regenerating fibers expressing embryonic MHC occurred, whereas IIx/b fibers were decreased. In the old mdx group, Po underwent a further reduction to 25% of control, and there was a slowing of twitch kinetics along with markedly increased diaphragm endurance. These changes were associated with an approximate sevenfold increase in type I MHC fibers and virtual elimination of the IIx/b fiber population; there was no detectable embryonic MHC expression. We conclude that the mdx diaphragm responds to progressive muscle degeneration with transition to a slower phenotype associated with reduced power output and augmented muscle endurance. In the setting of progressive muscle fiber destruction, these changes may help preserve contractile function and promote greater survival of remaining muscle fibers by decreasing cellular energy requirements.

APA, Harvard, Vancouver, ISO, and other styles

9

Hui, Tiankun, Hongyang Jing, Tian Zhou, Peng Chen, Ziyang Liu, Xia Dong, Min Yan, et al. "Increasing LRP4 diminishes neuromuscular deficits in a mouse model of Duchenne muscular dystrophy." Human Molecular Genetics 30, no. 17 (May 13, 2021): 1579–90. http://dx.doi.org/10.1093/hmg/ddab135.

Full text

Abstract:

Abstract Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease characterized by progressive wasting of skeletal muscles. The neuromuscular junction (NMJ) is a synapse between motor neurons and skeletal muscle fibers, critical for the control of muscle contraction. The NMJ decline is observed in DMD patients, but the mechanism is unclear. LRP4 serves as a receptor for agrin, a proteoglycan secreted by motor neurons to induce NMJ, and plays a critical role in NMJ formation and maintenance. Interestingly, we found that protein levels of LRP4 were reduced both in muscles of the DMD patients and DMD model mdx mice. We explored whether increasing LRP4 is beneficial for DMD and crossed muscle-specific LRP4 transgenic mice with mdx mice (mdx; HSA-LRP4). The LRP4 transgene increased muscle strength, together with improved neuromuscular transmission in mdx mice. Furthermore, we found the LRP4 expression mitigated NMJ fragments and denervation in mdx mice. Mechanically, we showed that overexpression of LRP4 increased the activity of MuSK and expression of dystrophin-associated glycoprotein complex proteins in the mdx mice. Overall, our findings suggest that increasing LRP4 improves both function and structure of NMJ in the mdx mice and Agrin signaling might serve as a new therapeutic strategy in DMD.

APA, Harvard, Vancouver, ISO, and other styles

10

McARDLE, Anne, Timothy R. HELLIWELL, Geoffrey J. BECKETT, Mariana CATAPANO, Anthony DAVIS, and Malcolm J. JACKSON. "Effect of propylthiouracil-induced hypothyroidism on the onset of skeletal muscle necrosis in dystrophin-deficient mdx mice." Clinical Science 95, no. 1 (July 1, 1998): 83–89. http://dx.doi.org/10.1042/cs0950083.

Full text

Abstract:

1.Duchenne and Becker muscular dystrophies are X-linked disorders caused by defects in muscle dystrophin. The mdx mouse is an animal model for Duchenne muscular dystrophy which has a point mutation in the dystrophin gene, resulting in little (< 3%) or no expression of dystrophin in muscle. Mdx mice show a characteristic pattern of muscle necrosis and regeneration. Muscles are normal until the third postnatal week when widespread necrosis commences. This is followed by muscle regeneration, with the persistence of centrally nucleated fibres. 2.This work has examined the hypothesis that the onset of this muscle necrosis is associated with postnatal maturation of the thyroid endocrine system and that pharmacological inhibition of thyroid hormone synthesis delays the onset of muscle necrosis. 3.Serum T4 and T3 concentrations of mice were found to rise immediately before the onset of muscle necrosis in the mdx mouse, and induction of hypothyroidism by treatment of animals with propylthiouracil was found to delay the onset of muscle necrosis. 4.The results provide the first demonstration of experimental delay of muscle necrosis by manipulation of the endocrine system in muscle lacking dystrophin, and provide a novel insight into the way in which a lack of dystrophin interacts with postnatal development to precipitate muscle necrosis in the mdx mouse.

APA, Harvard, Vancouver, ISO, and other styles

11

Laws, Nicola, and Andrew Hoey. "Progression of kyphosis in mdx mice." Journal of Applied Physiology 97, no. 5 (November 2004): 1970–77. http://dx.doi.org/10.1152/japplphysiol.01357.2003.

Full text

Abstract:

Spinal deformity in the form of kyphosis or kyphoscoliosis occurs in most patients with Duchenne muscular dystrophy (DMD), a fatal X-linked disorder caused by an absence of the subsarcolemmal protein dystrophin. Mdx mice, which also lack dystrophin, show thoracolumbar kyphosis that progresses with age. We hypothesize that paraspinal and respiratory muscle weakness and fibrosis are associated with the progression of spinal deformity in this mouse model, and similar to DMD patients there is evidence of altered thoracic conformation and area. We measured kyphosis in mdx and age-matched control mice by monthly radiographs and the application of a novel radiographic index, the kyphotic index, similar to that used in boys with DMD. Kyphotic index became significantly less in mdx at 9 mo of age (3.58 ± 0.12 compared with 4.27 ± 0.04 in the control strain; P ≤ 0.01), indicating more severe kyphosis, and remained less from 10 to 17 mo of age. Thoracic area in 17-mo-old mdx was reduced by 14% compared with control mice ( P ≤ 0.05). Peak tetanic tension was significantly lower in mdx and fell 47% in old mdx latissimus dorsi muscles, 44% in intercostal strips, and 73% in diaphragm strips ( P ≤ 0.05). Fibrosis of these muscles and the longissimus dorsi, measured by hydroxyproline analysis and histological grading of picrosirius red-stained sections, was greater in mdx ( P < 0.05). We conclude that kyphotic index is a useful measure in mdx and other kyphotic mouse strains, and assessment of paralumbar and accessory respiratory muscles enhance understanding of spinal deformity in muscular dystrophy.

APA, Harvard, Vancouver, ISO, and other styles

12

Rouger, Karl, Martine Le Cunff, Marja Steenman, Marie-Claude Potier, Nathalie Gibelin, Claude A. Dechesne, and Jean J. Leger. "Global/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice." American Journal of Physiology-Cell Physiology 283, no. 3 (September 1, 2002): C773—C784. http://dx.doi.org/10.1152/ajpcell.00112.2002.

Full text

Abstract:

The mdx mouse is a model for human Duchenne muscular dystrophy (DMD), an X-linked degenerative disease of skeletal muscle tissue characterized by the absence of the dystrophin protein. The mdx mice display a much milder phenotype than DMD patients. After the first week of life when all mdx muscles evolve like muscles of young DMD patients, mdx hindlimb muscles substantially compensate for the lack of dystrophin, whereas mdx diaphragm muscle becomes progressively affected by the disease. We used cDNA microarrays to compare the expression profile of 1,082 genes, previously selected by a subtractive method, in control and mdx hindlimb and diaphragm muscles at 12 time points over the first year of the mouse life. We determined that 1) the dystrophin gene defect induced marked expression remodeling of 112 genes encoding proteins implicated in diverse muscle cell functions and 2) two-thirds of the observed transcriptomal anomalies differed between adult mdx hindlimb and diaphragm muscles. Our results showed that neither mdx diaphram muscle nor mdx hindlimb muscles evolve entirely like the human DMD muscles. This finding should be taken under consideration for the interpretation of future experiments using mdx mice as a model for therapeutic assays.

APA, Harvard, Vancouver, ISO, and other styles

13

Geissinge, H. D., and L. D. Rhodes. "Regenerating myofibers in tibialis anterior muscles of young ‘MDX’ mice." Proceedings, annual meeting, Electron Microscopy Society of America 45 (August 1987): 726–27. http://dx.doi.org/10.1017/s0424820100127943.

Full text

Abstract:

A recently discovered mouse model (‘mdx’) for muscular dystrophy in man may be of considerable interest, since the disease in ‘mdx’ mice is inherited by the same mode of inheritance (X-linked) as the human Duchenne (DMD) muscular dystrophy. Unlike DMD, which results in a situation in which the continual muscle destruction cannot keep up with abortive regenerative attempts of the musculature, and the sufferers of the disease die early, the disease in ‘mdx’ mice appears to be transient, and the mice do not die as a result of it. In fact, it has been reported that the severely damaged Tibialis anterior (TA) muscles of ‘mdx’ mice seem to display exceptionally good regenerative powers at 4-6 weeks, so much so, that these muscles are able to regenerate spontaneously up to their previous levels of physiological activity.

APA, Harvard, Vancouver, ISO, and other styles

14

Menke, A., and H. Jockusch. "Extent of shock-induced membrane leakage in human and mouse myotubes depends on dystrophin." Journal of Cell Science 108, no. 2 (February 1, 1995): 727–33. http://dx.doi.org/10.1242/jcs.108.2.727.

Full text

Abstract:

A lack of the cytoskeletal protein dystrophin causes muscle fiber necrosis in Duchenne/Becker muscular dystrophies (DMD/BMD) and in murine X-linked muscular dystrophy (MDX). However, no overt disease symptoms are observed in dystrophin-less cultured myotubes, and the biological function of dystrophin in normal muscle cells is still unknown. In this work, we have extended our studies on a model system, using hypoosmotic shock to determine stress resistance of muscle cells. In frozen sections of control human and mouse myotubes, dystrophin was shown to be localized at the cell periphery as in mature muscle fibers. Dystrophin-less DMD and MDX myotubes were more susceptible to hypoosmotic shock than controls, as monitored by the uptake of external horseradish peroxidase and release of the soluble enzymes creatinine kinase or pyruvate kinase and of radiolabelled proteins. Control experiments indicated that this difference is not due to differences in metabolism or ion fluxes. Treatment with cytochalasin D drastically increased the shock sensitivity of myotubes and abolished the difference between dystrophin-less and control cells. These results lend further support to the suggested stabilizing role of dystrophin in the context of the membrane-cytoskeletal complex.

APA, Harvard, Vancouver, ISO, and other styles

15

Gibson, A. J., J. Karasinski, J. Relvas, J. Moss, T. G. Sherratt, P. N. Strong, and D. J. Watt. "Dermal fibroblasts convert to a myogenic lineage in mdx mouse muscle." Journal of Cell Science 108, no. 1 (January 1, 1995): 207–14. http://dx.doi.org/10.1242/jcs.108.1.207.

Full text

Abstract:

Duchenne muscular dystrophy is a primary muscle disease that manifests itself in young boys as a result of a defect in a gene located on the X-chromosome. This gene codes for dystrophin, a normal muscle protein that is located beneath the sarcolemma of muscle fibres. Therapies to alleviate this disease have centred on implanting normal muscle precursor cells into dystrophic fibres to compensate for the lack of this gene and its product. To date, donor cells for implantation in such therapy have been of myogenic origin, derived from paternal biopsies. Success in human muscle, however, has been limited and may reflect immune rejection problems. To overcome this problem the patient's own myogenic cells, with the dystrophin gene inserted, could be used, but this could lead to other problems, since these cells are those that are functionally compromised by the disease. Here, we report the presence of high numbers of dystrophin-positive fibres after implanting dermal fibroblasts from normal mice into the muscle of the mdx mouse-the genetic homologue of Duchenne muscular dystrophy. Dystrophin-positive fibres were also abundant in mdx muscle following the implantation of cloned dermal fibroblasts from the normal mouse. Our results suggest the in vivo conversion of these non-myogenic cells to the myogenic pathway resulting in the formation of dystrophin-positive muscle fibres in the deficient host. The use of dermal fibroblasts may provide an alternative approach to the previously attempted myoblast transfer therapy, which in human trials has yielded disappointing results.

APA, Harvard, Vancouver, ISO, and other styles

16

Bujold, Mathieu, Nicolas Caron, Goeffrey Camiran, Santwana Mukherjee, Paul D. Allen, Jacques P. Tremblay, and Yaming Wang. "Autotransplantation in mdx Mice of mdx Myoblasts Genetically Corrected by an HSV-1 Amplicon Vector." Cell Transplantation 11, no. 8 (November 2002): 759–67. http://dx.doi.org/10.3727/000000002783985297.

Full text

Abstract:

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder, characterized by a lack of dystrophin. To eliminate the need for immunosuppressive drugs, transplantation of genetically modified autologous myoblasts has been proposed as a possible therapy for this myopathy. An HSV-1 amplicon vector (HSVDGN), containing a 17.3-kb full-length MCK-driven mouse dystrophin cDNA, an eGFP gene, and a neomycin resistance gene driven by CMV or SV40 promoters, respectively, was constructed and used to transduce mdx primary myoblasts. The presence of the eGFP and neomycin resistance genes facilitated the evaluation of the initial transduction efficiency and the permanent transduction frequency. At low multiplicities of infection (MOI 1–5), the majority of myoblasts (60–90%) expressed GFP. The GFP-positive mdx myoblasts were sorted by FACS and selected with neomycin (300 μg/ml) for 2 weeks. Up to 2% of initially infected mdx myoblasts stably expressed the three transgenes without further selection at that time. These altered cells were grafted into the tibialis anterior muscles of 18 mdx mice. Some of the mice were immunosuppressed with FK506 due to the anticipation that eGFP and the product of neomycin resistance gene might be immunogenic. One month after transplantation, numerous muscle fibers expressing mouse dystrophin were detected by immunohistochemistry, in both immunosuppressed (10–50%) and nonimmunosuppressed (5–25%) mdx mice. Our results demonstrated the capability of permanently expressing a full-length dystrophin in dystrophic myoblasts with HSV-1 amplicon vector and raised the possibility of an eventual treatment of DMD based on the transplantation of genetically modified autologous myoblasts.

APA, Harvard, Vancouver, ISO, and other styles

17

Chao, D. S., J. R. Gorospe, J. E. Brenman, J. A. Rafael, M. F. Peters, S. C. Froehner, E. P. Hoffman, J. S. Chamberlain, and D. S. Bredt. "Selective loss of sarcolemmal nitric oxide synthase in Becker muscular dystrophy." Journal of Experimental Medicine 184, no. 2 (August 1, 1996): 609–18. http://dx.doi.org/10.1084/jem.184.2.609.

Full text

Abstract:

Becker muscular dystrophy is an X-linked disease due to mutations of the dystrophin gene. We now show that neuronal-type nitric oxide synthase (nNOS), an identified enzyme in the dystrophin complex, is uniquely absent from skeletal muscle plasma membrane in many human Becker patients and in mouse models of dystrophinopathy. An NH2-terminal domain of nNOS directly interacts with alpha 1-syntrophin but not with other proteins in the dystrophin complex analyzed. However, nNOS does not associate with alpha 1-syntrophin on the sarcolemma in transgenic mdx mice expressing truncated dystrophin proteins. This suggests a ternary interaction of nNOS, alpha 1-syntrophin, and the central domain of dystrophin in vivo, a conclusion supported by developmental studies in muscle. These data indicate that proper assembly of the dystrophin complex is dependent upon the structure of the central rodlike domain and have implications for the design of dystrophin-containing vectors for gene therapy.

APA, Harvard, Vancouver, ISO, and other styles

18

Kwak, Dongmin, Guoxian Wei, LaDora V. Thompson, and Jong-Hee Kim. "Short-Term ONX-0914 Administration: Performance and Muscle Phenotype in Mdx Mice." International Journal of Environmental Research and Public Health 17, no. 14 (July 19, 2020): 5211. http://dx.doi.org/10.3390/ijerph17145211.

Full text

Abstract:

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease. Although the lack of dystrophin protein is the primary defect responsible for the development of DMD, secondary disease complications such as persistent inflammation contribute greatly to the pathogenesis and the time-dependent progression of muscle destruction. The immunoproteasome is a potential therapeutic target for conditions or diseases mechanistically linked to inflammation. In this study, we explored the possible effects of ONX-0914 administration, an inhibitor specific for the immunoproteasome subunit LMP7 (ß5i), on motor performance, muscular pathology and protein degradation in 7-week old MDX mice, an age when the dystrophic muscles show extensive degeneration and regeneration. ONX-0914 (10 mg/kg) was injected subcutaneously on Day 2, 4, and 6. The mice were evaluated for physical performance (walking speed and strength) on Day 1 and 8. We show that this short-term treatment of ONX-0914 in MDX mice did not alter strength nor walking speed. The physical performance findings were consistent with no change in muscle inflammatory infiltration, percentage of central nuclei and proteasome content. Taken together, muscle structure and function in the young adult MDX mouse model are not altered with ONX-0914 treatment, indicating the administration of ONX-0914 during this critical time period does not exhibit any detrimental effects and may be an effective treatment of secondary complications of muscular dystrophy after further investigations.

APA, Harvard, Vancouver, ISO, and other styles

19

Yanay, Nurit, Moran Elbaz, Jenya Konikov-Rozenman, Sharona Elgavish, Yuval Nevo, Yakov Fellig, Malcolm Rabie, Stella Mitrani-Rosenbaum, and Yoram Nevo. "Pax7, Pax3 and Mamstr genes are involved in skeletal muscle impaired regeneration of dy2J/dy2J mouse model of Lama2-CMD." Human Molecular Genetics 28, no. 20 (July 26, 2019): 3369–90. http://dx.doi.org/10.1093/hmg/ddz180.

Full text

Abstract:

Abstract Congenital muscular dystrophy type-1A (Lama2-CMD) and Duchenne muscular dystrophy (DMD) result from deficiencies of laminin-α2 and dystrophin proteins, respectively. Although both proteins strengthen the sarcolemma, they are implicated in clinically distinct phenotypes. We used RNA-deep sequencing (RNA-Seq) of dy2J/dy2J, Lama2-CMD mouse model, skeletal muscle at 8 weeks of age to elucidate disease pathophysiology. This study is the first report of dy2J/dy2J model whole transcriptome profile. RNA-Seq of the mdx mouse model of DMD and wild-type (WT) mouse was carried as well in order to enable a novel comparison of dy2J/dy2J to mdx. A large group of shared differentially expressed genes (DEGs) was found in dy2J/dy2J and mdx models (1834 common DEGs, false discovery rate [FDR] < 0.05). Enrichment pathway analysis using ingenuity pathway analysis showed enrichment of inflammation, fibrosis, cellular movement, migration and proliferation of cells, apoptosis and necrosis in both mouse models (P-values 3E-10–9E-37). Via canonical pathway analysis, actin cytoskeleton, integrin, integrin-linked kinase, NF-kB, renin–angiotensin, epithelial–mesenchymal transition, and calcium signaling were also enriched and upregulated in both models (FDR < 0.05). Interestingly, significant downregulation of Pax7 was detected in dy2J/dy2J compared to upregulation of this key regeneration gene in mdx mice. Pax3 and Mamstr genes were also downregulated in dy2J/dy2J compared to WT mice. These results may explain the distinct disease course and severity in these models. While the mdx model at that stage shows massive regeneration, the dy2J/dy2J shows progressive dystrophic process. Our data deepen our understanding of the molecular pathophysiology and suggest new targets for additional therapies to upregulate regeneration in Lama2-CMD.

APA, Harvard, Vancouver, ISO, and other styles

20

Rae, Mark G., and Dervla O'Malley. "Cognitive dysfunction in Duchenne muscular dystrophy: a possible role for neuromodulatory immune molecules." Journal of Neurophysiology 116, no. 3 (September 1, 2016): 1304–15. http://dx.doi.org/10.1152/jn.00248.2016.

Full text

Abstract:

Duchenne muscular dystrophy (DMD) is an X chromosome-linked disease characterized by progressive physical disability, immobility, and premature death in affected boys. Underlying the devastating symptoms of DMD is the loss of dystrophin, a structural protein that connects the extracellular matrix to the cell cytoskeleton and provides protection against contraction-induced damage in muscle cells, leading to chronic peripheral inflammation. However, dystrophin is also expressed in neurons within specific brain regions, including the hippocampus, a structure associated with learning and memory formation. Linked to this, a subset of boys with DMD exhibit nonprogressing cognitive dysfunction, with deficits in verbal, short-term, and working memory. Furthermore, in the genetically comparable dystrophin-deficient mdx mouse model of DMD, some, but not all, types of learning and memory are deficient, and specific deficits in synaptogenesis and channel clustering at synapses has been noted. Little consideration has been devoted to the cognitive deficits associated with DMD compared with the research conducted into the peripheral effects of dystrophin deficiency. Therefore, this review focuses on what is known about the role of full-length dystrophin (Dp427) in hippocampal neurons. The importance of dystrophin in learning and memory is assessed, and the potential importance that inflammatory mediators, which are chronically elevated in dystrophinopathies, may have on hippocampal function is also evaluated.

APA, Harvard, Vancouver, ISO, and other styles

21

Lessa, Thais Borges, Rafael Cardoso Carvalho, Júlio David Spagnolo, Luis Claudio Lopes Correia da Silva, Silvia Renata Gaido Cortopassi, and Carlos Eduardo Ambrósio. "Laparoscopic guided local injection in the X-linked muscular dystrophy mouse (mdx) diaphragm. An advance in experimental therapies for Duchenne Muscular Dystrophy." Acta Cirurgica Brasileira 29, no. 11 (November 2014): 715–20. http://dx.doi.org/10.1590/s0102-86502014001800004.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

Dell'Agnola, Chiara, Zejing Wang, Rainer Storb, Stephen J. Tapscott, Christian S. Kuhr, Stephen D. Hauschka, Richard S. Lee, et al. "Hematopoietic stem cell transplantation does not restore dystrophin expression in Duchenne muscular dystrophy dogs." Blood 104, no. 13 (December 15, 2004): 4311–18. http://dx.doi.org/10.1182/blood-2004-06-2247.

Full text

Abstract:

Abstract Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene on the X-chromosome that result in skeletal and cardiac muscle damage and premature death. Studies in mice, including the mdx mouse model of DMD, have demonstrated that circulating bone marrow–derived cells can participate in skeletal muscle regeneration, but the potential clinical utility of treating human DMD by allogeneic marrow transplantation from a healthy donor remains unknown. To assess whether allogeneic hematopoietic cell transplantation (HCT) provides clinically relevant levels of donor muscle cell contribution in dogs with canine X-linked muscular dystrophy (c-xmd), 7 xmd dogs were given hematopoietic cell (HC) transplants from nonaffected littermates. Compared with the pretransplantation baseline, the number of dystrophin-positive fibers and the amount of wild-type dystrophin RNA did not increase after HCT, with observation periods ranging from 28 to 417 days. Similar results were obtained when the recipient dogs were given granulocyte colony-stimulating factor (G-CSF) after their initial transplantation to mobilize the cells. Despite successful allogeneic HCT and a permissive environment for donor muscle engraftment, there was no detectable contribution of bone marrow–derived cells to either skeletal muscle or muscle precursor cells assayed by clonal analyses at a level of sensitivity that should detect as little as 0.1% donor contribution.

APA, Harvard, Vancouver, ISO, and other styles

23

Chan, S., S. I. Head, and J. W. Morley. "Branched fibers in dystrophic mdx muscle are associated with a loss of force following lengthening contractions." American Journal of Physiology-Cell Physiology 293, no. 3 (September 2007): C985—C992. http://dx.doi.org/10.1152/ajpcell.00128.2007.

Full text

Abstract:

We demonstrated that the susceptibility of skeletal muscle to injury from lengthening contractions in the dystrophin-deficient mdx mouse is directly linked with the extent of fiber branching within the muscles and that both parameters increase as the mdx animal ages. We subjected isolated extensor digitorum longus muscles to a lengthening contraction protocol of 15% strain and measured the resulting drop in force production (force deficit). We also examined the morphology of individual muscle fibers. In mdx mice 1–2 mo of age, 17% of muscle fibers were branched, and the force deficit of 7% was not significantly different from that of age-matched littermate controls. In mdx mice 6–7 mo of age, 89% of muscle fibers were branched, and the force deficit of 58% was significantly higher than the 25% force deficit of age-matched littermate controls. These data demonstrated an association between the extent of branching and the greater vulnerability to contraction-induced injury in the older fast-twitch dystrophic muscle. Our findings demonstrate that fiber branching may play a role in the pathogenesis of muscular dystrophy in mdx mice, and this could affect the interpretation of previous studies involving lengthening contractions in this animal.

APA, Harvard, Vancouver, ISO, and other styles

24

Siemionow, Maria, M. Malik, P. Langa, J. Cwykiel, S. Brodowska, and A. Heydemann. "Cardiac Protection after Systemic Transplant of Dystrophin Expressing Chimeric (DEC) Cells to the mdx Mouse Model of Duchenne Muscular Dystrophy." Stem Cell Reviews and Reports 15, no. 6 (October 15, 2019): 827–41. http://dx.doi.org/10.1007/s12015-019-09916-0.

Full text

Abstract:

Abstract Duchenne Muscular Dystrophy (DMD) is a progressive lethal disease caused by X-linked mutations of the dystrophin gene. Dystrophin deficiency clinically manifests as skeletal and cardiac muscle weakness, leading to muscle wasting and premature death due to cardiac and respiratory failure. Currently, no cure exists. Since heart disease is becoming a leading cause of death in DMD patients, there is an urgent need to develop new more effective therapeutic strategies for protection and improvement of cardiac function. We previously reported functional improvements correlating with dystrophin restoration following transplantation of Dystrophin Expressing Chimeric Cells (DEC) of myoblast origin in the mdx and mdx/scid mouse models. Here, we confirm positive effect of DEC of myoblast (MBwt/MBmdx) and mesenchymal stem cells (MBwt/MSCmdx) origin on protection of cardiac function after systemic DEC transplant. Therapeutic effect of DEC transplant (0.5 × 106) was assessed by echocardiography at 30 and 90 days after systemic-intraosseous injection to the mdx mice. At 90 days post-transplant, dystrophin expression in cardiac muscles of DEC injected mice significantly increased (15.73% ± 5.70 –MBwt/MBmdx and 5.22% ± 1.10 – MBwt/MSCmdx DEC) when compared to vehicle injected controls (2.01% ± 1.36) and, correlated with improved ejection fraction and fractional shortening on echocardiography. DEC lines of MB and MSC origin introduce a new promising approach based on the combined effects of normal myoblasts with dystrophin delivery capacities and MSC with immunomodulatory properties. Our study confirms feasibility and efficacy of DEC therapy on cardiac function and represents a novel therapeutic strategy for cardiac protection and muscle regeneration in DMD.

APA, Harvard, Vancouver, ISO, and other styles

25

Barraza-Flores, Pamela, Tatiana M. Fontelonga, Ryan D. Wuebbles, Hailey J. Hermann, Andreia M. Nunes, Joe N. Kornegay, and Dean J. Burkin. "Laminin-111 protein therapy enhances muscle regeneration and repair in the GRMD dog model of Duchenne muscular dystrophy." Human Molecular Genetics 28, no. 16 (April 24, 2019): 2686–95. http://dx.doi.org/10.1093/hmg/ddz086.

Full text

Abstract:

Abstract Duchenne muscular dystrophy (DMD) is a devastating X-linked disease affecting ~1 in 5000 males. DMD patients exhibit progressive muscle degeneration and weakness, leading to loss of ambulation and premature death from cardiopulmonary failure. We previously reported that mouse Laminin-111 (msLam-111) protein could reduce muscle pathology and improve muscle function in the mdx mouse model for DMD. In this study, we examined the ability of msLam-111 to prevent muscle disease progression in the golden retriever muscular dystrophy (GRMD) dog model of DMD. The msLam-111 protein was injected into the cranial tibial muscle compartment of GRMD dogs and muscle strength and pathology were assessed. The results showed that msLam-111 treatment increased muscle fiber regeneration and repair with improved muscle strength and reduced muscle fibrosis in the GRMD model. Together, these findings support the idea that Laminin-111 could serve as a novel protein therapy for the treatment of DMD.

APA, Harvard, Vancouver, ISO, and other styles

26

Sano, M., Y. Wada, K. Ii, E. Kominami, N. Katunuma, and H. Tsukagoshi. "Immunolocalization of cathepsins B, H and L in skeletal muscle of X-linked muscular dystrophy (mdx) mouse." Acta Neuropathologica 75, no. 3 (1988): 217–25. http://dx.doi.org/10.1007/bf00690529.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Klymiuk, N., C. Thirion, K. Burkhardt, A. Wuensch, S. Krause, A. Richter, B. Kessler, et al. "238 TAILORED PIG MODEL OF DUCHENNE MUSCULAR DYSTROPHY." Reproduction, Fertility and Development 24, no. 1 (2012): 231. http://dx.doi.org/10.1071/rdv24n1ab238.

Full text

Abstract:

Duchenne muscular dystrophy (DMD) is one of the most common genetic diseases in humans, affecting 1 in 3500 boys. It is characterised by progressive muscle weakness and wasting due to mutations in the dystrophin (DMD) gene resulting in absence of dystrophin protein in skeletal muscle. Although curative treatments are currently not available, genetic and pharmacological approaches are under investigation including early-phase clinical trials. Existing animal models in different species (e.g. mdx mouse, GRMD dog) have been instrumental to understand the pathophysiology of DMD, but have several limitations. Importantly, the causative point mutations (mdx mouse: nonsense mutation; GRMD dog: splice mutation) are different from the most common human mutations (out-of-frame deletion of one or several exons of the DMD gene). We used gene targeting in somatic cells and nuclear transfer to generate a genetically tailored pig model of DMD. A bacterial artificial chromosome (BAC) from the porcine DMD gene was modified by recombineering to replace exon 52, resulting in a frame shift in the transcript. Modified BAC were transfected into male neonatal kidney cells, which were screened by quantitative polymerase chain reaction for replacement of exon 52 in the X-linked DMD gene. Eight of 436 cell clones were successfully targeted and 2 of them were used for nuclear transfer. For each of the cell clones, a pregnancy was established by transfer of cloned embryos into recipient gilts. Four piglets of the first litter were live born and killed within 48 h and tissue samples were processed for histological characterisation. Two piglets of the second litter died during birth due to obstetric complications, whereas the other 2 piglets were delivered by Caesarean section and raised in an artificial feeding system. Their serum creatine kinase (CK) levels were grossly elevated. Although both piglets showed reduced mobility compared with age-matched controls, they were able to move and feed on their own. Immunofluorescence staining of dystrophin was negative in muscle fibres of DMD mutant piglets and the complete absence of dystrophin protein was confirmed by immunoblot analysis. Histological examination of biceps femoris muscle from DMD mutant pigs showed a degenerative myopathy with fibre size variation, rounded fibres, central nuclei, fibrosis and fatty replacement of muscle tissue mimicking the hallmarks of the human disease. In conclusion, we generated the first pig model for a genetic muscle disease. The DMD mutant pig appears to be a bona fide model of the human dystrophy as ascertained by absence of the dystrophin protein, elevated serum CK levels and early degenerative changes on muscle histology. Because deletion of exon 52 is one of the most frequent mutations found in human DMD, the exon 52 mutated DMD pig represents an excellent model for testing targeted genetic treatments. This study was supported by the Bayerische Forschungsstiftung.

APA, Harvard, Vancouver, ISO, and other styles

28

Selsby, Joshua, Klara Pendrak, Monica Zadel, Zuozhen Tian, Jennifer Pham, Ted Carver, Pedro Acosta, Elisabeth Barton, and H. Lee Sweeney. "Leupeptin-based inhibitors do not improve the mdx phenotype." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 299, no. 5 (November 2010): R1192—R1201. http://dx.doi.org/10.1152/ajpregu.00586.2009.

Full text

Abstract:

Calpain activation has been implicated in the disease pathology of Duchenne muscular dystrophy. Inhibition of calpain has been proposed as a promising therapeutic target, which could lessen the protein degradation and prevent progressive fibrosis. At the same time, there are conflicting reports as to whether elevation of calpastatin, an endogenous calpain inhibitor, alters pathology. We compared the effects of pharmacological calpain inhibition in the mdx mouse using leupeptin and a proprietary compound (C101) that linked the inhibitory portion of leupeptin to carnitine (to increase uptake into muscle). Administration of C101 for 4 wk did not improve muscle histology, function, or serum creatine kinase levels in mdx mice. Mdx mice injected daily with leupeptin (36 mg/kg) for 6 mo also failed to show improved muscle function, histology, or creatine kinase levels. Biochemical analysis revealed that leupeptin administration caused an increase in m-calpain autolysis and proteasome activity, yet calpastatin levels were similar between treated and untreated mdx mice. These data demonstrate that pharmacological inhibition of calpain is not a promising intervention for the treatment of Duchenne muscular dystrophy due to the ability of skeletal muscle to counter calpain inhibitors by increasing multiple degradative pathways.

APA, Harvard, Vancouver, ISO, and other styles

29

Dudley, Roy W. R., Maya Khairallah, Shawn Mohammed, Larry Lands, Christine Des Rosiers, and Basil J. Petrof. "Dynamic responses of the glutathione system to acute oxidative stress in dystrophic mouse (mdx) muscles." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 291, no. 3 (September 2006): R704—R710. http://dx.doi.org/10.1152/ajpregu.00031.2006.

Full text

Abstract:

The precise mechanisms underlying skeletal muscle damage in Duchenne muscular dystrophy (DMD) remain ill-defined. Functional ischemia during muscle activation, with subsequent reperfusion during rest, has been documented. Therefore, one possibility is the presence of increased oxidative stress. We applied a model of acute hindlimb ischemia/reperfusion (I/R) in mdx mice (genetic homolog of DMD) to evaluate dynamic in vivo responses of dystrophic muscles to this form of oxidative stress. Before the application of I/R, mdx muscles showed: 1) decreased levels of total glutathione (GSH) with an increased oxidized (GSSG)-to-reduced (GSH) glutathione ratio; 2) greater activity of the GSH-metabolizing enzymes glutathione peroxidase (GPx) and glutathione reductase; and 3) lower activity levels of NADP-linked isocitrate dehydrogenase (ICDH) and aconitase, two metabolic enzymes that are sensitive to inactivation by oxidative stress and also implicated in GSH regeneration. Interestingly, nondystrophic muscles subjected to I/R exhibited similar changes in total glutathione, GSSG/GSH, GPx, ICDH, and aconitase. In contrast, all of the above remained stable in mdx muscles subjected to I/R. Taken together, these results suggest that mdx muscles are chronically subjected to increased oxidative stress, leading to adaptive changes that attempt to protect (although only in part) the dystrophic muscles from acute I/R-induced oxidative stress. In addition, mdx muscles show significant impairment of the redox-sensitive metabolic enzymes ICDH and aconitase, which may further contribute to contractile dysfunction in dystrophic muscles.

APA, Harvard, Vancouver, ISO, and other styles

30

Peters, J., S. T. Ball, D. J. Charles, W. Pretsch, Grahame Bulfield, D. Miller, and V. M. Chapman. "The localization of G6pd, glucose-6-phosphate dehydrogenase, and mdx, muscular dystrophy in the mouse X chromosome." Genetical Research 52, no. 3 (December 1988): 195–201. http://dx.doi.org/10.1017/s0016672300027658.

Full text

Abstract:

SummaryA low activity mutant of glucose-6-phosphate dehydrogenase, G6pda-m1Neu has been used to position G6pd in the mouse X chromosome. Linkage tests with tabby, Ta and harlequin, Hq, indicate a likely gene order of Hq–G6pd–Ta. Muscular dystrophy, mdx, has been located by two-and three-point crosses using Hprt, Pgk-1 and Moblo and suggest a gene order of Hprt–mdx–Pgk-1–Moblo. Together with existing linkage data a tentative order for the seven loci is Hq–Hprt–G6pd–mdx–Ta–Pgk-1–Moblo. The relative positions of G6pd and mdx have not been directly tested and G6pd is assigned provisionally proximal to mdx. In the three point test using Hq, G6pd and Ta the recombination frequency found between Hq and Ta was 9·9 ± 2·6%, substantially less than the value of 20·5 ± 2·1% reported by Isaacson et al. (1974).

APA, Harvard, Vancouver, ISO, and other styles

31

Meyers, Tatyana A., Jackie A. Heitzman, and DeWayne Townsend. "DMD carrier model with mosaic dystrophin expression in the heart reveals complex vulnerability to myocardial injury." Human Molecular Genetics 29, no. 6 (January 24, 2020): 944–54. http://dx.doi.org/10.1093/hmg/ddaa015.

Full text

Abstract:

Abstract Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease that causes progressive muscle wasting and cardiomyopathy. This X-linked disease results from mutations of the DMD allele on the X-chromosome resulting in the loss of expression of the protein dystrophin. Dystrophin loss causes cellular dysfunction that drives the loss of healthy skeletal muscle and cardiomyocytes. As gene therapy strategies strive toward dystrophin restoration through micro-dystrophin delivery or exon skipping, preclinical models have shown that incomplete restoration in the heart results in heterogeneous dystrophin expression throughout the myocardium. This outcome prompts the question of how much dystrophin restoration is sufficient to rescue the heart from DMD-related pathology. Female DMD carrier hearts can shed light on this question, due to their mosaic cardiac dystrophin expression resulting from random X-inactivation. In this work, a dystrophinopathy carrier mouse model was derived by breeding male or female dystrophin-null mdx mice with a wild type mate. We report that these carrier hearts are significantly susceptible to injury induced by one or multiple high doses of isoproterenol, despite expressing ~57% dystrophin. Importantly, only carrier mice with dystrophic mothers showed mortality after isoproterenol. These findings indicate that dystrophin restoration in approximately half of the heart still allows for marked vulnerability to injury. Additionally, the discovery of divergent stress-induced mortality based on parental origin in mice with equivalent dystrophin expression underscores the need for better understanding of the epigenetic, developmental, and even environmental factors that may modulate vulnerability in the dystrophic heart.

APA, Harvard, Vancouver, ISO, and other styles

32

Nguyen, T. M., J. M. Ellis, D. R. Love, K. E. Davies, K. C. Gatter, G. Dickson, and G. E. Morris. "Localization of the DMDL gene-encoded dystrophin-related protein using a panel of nineteen monoclonal antibodies: presence at neuromuscular junctions, in the sarcolemma of dystrophic skeletal muscle, in vascular and other smooth muscles, and in proliferating brain cell lines." Journal of Cell Biology 115, no. 6 (December 15, 1991): 1695–700. http://dx.doi.org/10.1083/jcb.115.6.1695.

Full text

Abstract:

mAbs have been raised against different epitopes on the protein product of the DMDL gene, which is an autosomal homologue of the X-linked DMD gene for dystrophin. These antibodies provide direct evidence that DMDL protein is localized near acetylcholine receptors at neuromuscular junctions in normal and mdx mouse intercostal muscle. The primary location in tissues other than skeletal muscle is smooth muscle, especially in the vascular system, which may account for the wide tissue distribution previously demonstrated by Western blotting. The DMDL protein was undetectable in the nonjunctional sarcolemma of normal human muscle, but was observed in nonjunctional sarcolemma of Duchenne muscular dystrophy patients, where dystrophin itself is absent or greatly reduced. The expression of DMDL protein is not restricted to smooth and skeletal muscle, however, since relatively large amounts are present in transformed brain cell lines of both glial and Schwann cell origin. This contrasts with the low levels of DMDL protein in adult brain tissue.

APA, Harvard, Vancouver, ISO, and other styles

33

Al-Mshhdani, Basma A., Miranda D. Grounds, Peter G. Arthur, and Jessica R. Terrill. "A Blood Biomarker for Duchenne Muscular Dystrophy Shows That Oxidation State of Albumin Correlates with Protein Oxidation and Damage in Mdx Muscle." Antioxidants 10, no. 8 (August 3, 2021): 1241. http://dx.doi.org/10.3390/antiox10081241.

Full text

Abstract:

Duchenne muscular dystrophy (DMD) is a severe X-linked muscle wasting disease with no cure. While the precise mechanisms of progressive dystropathology remain unclear, oxidative stress caused by excessive generation of oxidants is strongly implicated. Blood biomarkers that could track oxidant levels in tissues would be valuable to measure the effectiveness of clinical treatments for DMD; our research has focused on developing such biomarkers. One target of oxidants that has the potential to be harnessed as a clinical biomarker is the thiol side chain of cysteine 34 (Cys34) of the blood protein albumin. This study using the mdx mouse model of DMD shows that in plasma, albumin Cys34 undergoes thiol oxidation and these changes correlate with levels of protein thiol oxidation and damage of the dystrophic muscles. A comparison with the commonly used biomarker protein carbonylation, confirmed that albumin thiol oxidation is the more sensitive plasma biomarker of oxidative stress occurring in muscle tissue. We show that plasma albumin oxidation reflects muscle dystropathology, as increased after exercise and decreased after taurine treatment of mdx mice. These data support the use of albumin thiol oxidation as a blood biomarker of dystropathology to assist with advancing clinical development of therapies for DMD.

APA, Harvard, Vancouver, ISO, and other styles

34

Hagiwara, Y., Y. Nishina, M. Imamura, M. Yoshida, T. Kikuchi, I. Nonaka, and H. Yorifuji. "Caveolin-3 in skeletal muscle fibres of Duchenne muscular dystrophy and mdx mouse." Neuromuscular Disorders 7, no. 6-7 (September 1997): 436. http://dx.doi.org/10.1016/s0960-8966(97)87201-x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Xin, Can, Xiangyu Chu, Wenzhong Wei, Biao Kuang, Yiqing Wang, Ying Tang, Jincao Chen, Hongbo You, Chengwen Li, and Bing Wang. "Combined gene therapy via VEGF and mini-dystrophin synergistically improves pathologies in temporalis muscle of dystrophin/utrophin double knockout mice." Human Molecular Genetics 30, no. 14 (May 13, 2021): 1349–59. http://dx.doi.org/10.1093/hmg/ddab120.

Full text

Abstract:

Abstract Duchenne muscular dystrophy (DMD) is a severe X-linked inherited muscular disorder characterized by the loss of dystrophin. We have previously shown that monogene therapy using the mini-dystrophin gene improves muscle function in DMD. However, chronic inflammation plays an important role in progressive muscle degeneration in DMD as well. Vascular endothelial growth factor (VEGF) has been used to enhance muscle vasculature, reduce local inflammation and improve DMD muscle function. Temporalis muscles are the key skeletal muscles for mastication and loss of their function negatively affects DMD patient quality of life by reducing nutritional intake, but little is known about the pathology and treatment of the temporalis muscle in DMD. In this work, we tested the hypothesis that the combined delivery of the human mini-dystrophin and human VEGF genes to the temporalis muscles using separate recombinant adeno-associated viral (rAAV) vectors will synergistically improve muscle function and pathology in adult male dystrophin/utrophin double-knockout (mdx/utrn+/−) mice. The experimental mice were divided into four groups including: dystrophin + VEGF combined, dystrophin only, VEGF only and PBS control. After 2 months, gene expression and histological analysis of the temporalis muscles showed a synergistic improvement in temporalis muscle pathology and function coincident with increased restoration of dystrophin-associated protein complexes and nNOS in the dystrophin + VEGF combined group. We also observed significantly reduced inflammatory cell infiltration, central nucleation, and fibrosis in the dystrophin + VEGF combined group. We have demonstrated the efficacy of combined rAAV-mediated dystrophin and VEGF treatment of temporalis muscles in a DMD mouse model.

APA, Harvard, Vancouver, ISO, and other styles

36

Carnwath, Joseph W., and David M. Shotton. "Muscular dystrophy in the mdx mouse: Histopathology of the soleus and extensor digitorum longus muscles." Journal of the Neurological Sciences 80, no. 1 (August 1987): 39–54. http://dx.doi.org/10.1016/0022-510x(87)90219-x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Dowling, Paul, Margit Zweyer, Maren Raucamp, Michael Henry, Paula Meleady, Dieter Swandulla, and Kay Ohlendieck. "Dataset on the mass spectrometry-based proteomic profiling of the kidney from wild type and the dystrophic mdx-4cv mouse model of X-linked muscular dystrophy." Data in Brief 28 (February 2020): 105067. http://dx.doi.org/10.1016/j.dib.2019.105067.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Ieronimakis, Nicholas, Aislinn L. Hays, Kajohnkiart Janebodin, William M. Mahoney, Jeremy S. Duffield, Mark W. Majesky, and Morayma Reyes. "Coronary adventitial cells are linked to perivascular cardiac fibrosis via TGFβ1 signaling in the mdx mouse model of Duchenne muscular dystrophy." Journal of Molecular and Cellular Cardiology 63 (October 2013): 122–34. http://dx.doi.org/10.1016/j.yjmcc.2013.07.014.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Watt, Diana J., Janusz Karasinski, and Marjorie A. England. "Migration of lacZ positive cells from the tibialis anterior to the extensor digitorum longus muscle of the X-linked muscular dystrophic (mdx) mouse." Journal of Muscle Research and Cell Motility 14, no. 1 (February 1993): 121–32. http://dx.doi.org/10.1007/bf00132186.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

GILLIS, J. M. "Membrane abnormalities and Ca homeostasis in muscles of the mdx mouse, an animal model of the Duchenne muscular dystrophy: a review." Acta Physiologica Scandinavica 156, no. 3 (March 1996): 397–406. http://dx.doi.org/10.1046/j.1365-201x.1996.201000.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Iyer, Shama R., Sameer B. Shah, Ana P. Valencia, Martin F. Schneider, Erick O. Hernández-Ochoa, Joseph P. Stains, Silvia S. Blemker, and Richard M. Lovering. "Altered nuclear dynamics in MDX myofibers." Journal of Applied Physiology 122, no. 3 (March 1, 2017): 470–81. http://dx.doi.org/10.1152/japplphysiol.00857.2016.

Full text

Abstract:

Duchenne muscular dystrophy (DMD) is a genetic disorder in which the absence of dystrophin leads to progressive muscle degeneration and weakness. Although the genetic basis is known, the pathophysiology of dystrophic skeletal muscle remains unclear. We examined nuclear movement in wild-type (WT) and muscular dystrophy mouse model for DMD (MDX) (dystrophin-null) mouse myofibers. We also examined expression of proteins in the linkers of nucleoskeleton and cytoskeleton (LINC) complex, as well as nuclear transcriptional activity via histone H3 acetylation and polyadenylate-binding nuclear protein-1. Because movement of nuclei is not only LINC dependent but also microtubule dependent, we analyzed microtubule density and organization in WT and MDX myofibers, including the application of a unique 3D tool to assess microtubule core structure. Nuclei in MDX myofibers were more mobile than in WT myofibers for both distance traveled and velocity. MDX muscle shows reduced expression and labeling intensity of nesprin-1, a LINC protein that attaches the nucleus to the microtubule and actin cytoskeleton. MDX nuclei also showed altered transcriptional activity. Previous studies established that microtubule structure at the cortex is disrupted in MDX myofibers; our analyses extend these findings by showing that microtubule structure in the core is also disrupted. In addition, we studied malformed MDX myofibers to better understand the role of altered myofiber morphology vs. microtubule architecture in the underlying susceptibility to injury seen in dystrophic muscles. We incorporated morphological and microtubule architectural concepts into a simplified finite element mathematical model of myofiber mechanics, which suggests a greater contribution of myofiber morphology than microtubule structure to muscle biomechanical performance.NEW & NOTEWORTHY Microtubules provide the means for nuclear movement but show altered organization in the muscular dystrophy mouse model (MDX) (dystrophin-null) muscle. Here, MDX myofibers show increased nuclear movement, altered transcriptional activity, and altered linkers of nucleoskeleton and cytoskeleton complex expression compared with healthy myofibers. Microtubule architecture was incorporated in finite element modeling of passive stretch, revealing a role of fiber malformation, commonly found in MDX muscle. The results suggest that alterations in microtubule architecture in MDX muscle affect nuclear movement, which is essential for muscle function.

APA, Harvard, Vancouver, ISO, and other styles

42

Cozzoli, A., J. F. Rolland, R. F. Capogrosso, V. T. Sblendorio, V. Longo, S. Simonetti, B. Nico, and A. De Luca. "Evaluation of potential synergistic action of a combined treatment with alpha-methyl-prednisolone and taurine on the mdx mouse model of Duchenne muscular dystrophy." Neuropathology and Applied Neurobiology 37, no. 3 (February 22, 2011): 243–56. http://dx.doi.org/10.1111/j.1365-2990.2010.01106.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

43

Hirn, Carole, George Shapovalov, Olivier Petermann, Emmanuelle Roulet, and Urs T. Ruegg. "Nav1.4 Deregulation in Dystrophic Skeletal Muscle Leads to Na+ Overload and Enhanced Cell Death." Journal of General Physiology 132, no. 2 (July 14, 2008): 199–208. http://dx.doi.org/10.1085/jgp.200810024.

Full text

Abstract:

Duchenne muscular dystrophy (DMD) is a hereditary degenerative disease manifested by the absence of dystrophin, a structural, cytoskeletal protein, leading to muscle degeneration and early death through respiratory and cardiac muscle failure. Whereas the rise of cytosolic Ca2+ concentrations in muscles of mdx mouse, an animal model of DMD, has been extensively documented, little is known about the mechanisms causing alterations in Na+ concentrations. Here we show that the skeletal muscle isoform of the voltage-gated sodium channel, Nav1.4, which represents over 90% of voltage-gated sodium channels in muscle, plays an important role in development of abnormally high Na+ concentrations found in muscle from mdx mice. The absence of dystrophin modifies the expression level and gating properties of Nav1.4, leading to an increased Na+ concentration under the sarcolemma. Moreover, the distribution of Nav1.4 is altered in mdx muscle while maintaining the colocalization with one of the dystrophin-associated proteins, syntrophin α-1, thus suggesting that syntrophin is an important linker between dystrophin and Nav1.4. Additionally, we show that these modifications of Nav1.4 gating properties and increased Na+ concentrations are strongly correlated with increased cell death in mdx fibers and that both cell death and Na+ overload can be reversed by 3 nM tetrodotoxin, a specific Nav1.4 blocker.

APA, Harvard, Vancouver, ISO, and other styles

44

Shibuya, S., and Y. Wakayama. "Freeze-fracture studies of myofiber plasma membrane in X chromosome-linked muscular dystrophy (mdx) mice." Acta Neuropathologica 76, no. 2 (1988): 179–84. http://dx.doi.org/10.1007/bf00688102.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Nogami, Ken'ichiro, Yusuke Maruyama, Fusako Sakai-Takemura, Norio Motohashi, Ahmed Elhussieny, Michihiro Imamura, Satoshi Miyashita, et al. "Pharmacological activation of SERCA ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice." Human Molecular Genetics 30, no. 11 (April 5, 2021): 1006–19. http://dx.doi.org/10.1093/hmg/ddab100.

Full text

Abstract:

Abstract Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscular weakness because of the loss of dystrophin. Extracellular Ca2+ flows into the cytoplasm through membrane tears in dystrophin-deficient myofibers, which leads to muscle contracture and necrosis. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) takes up cytosolic Ca2+ into the sarcoplasmic reticulum, but its activity is decreased in dystrophic muscle. Here, we show that an allosteric SERCA activator, CDN1163, ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice. The administration of CDN1163 prevented exercise-induced muscular damage and restored mitochondrial function. In addition, treatment with CDN1163 for 7 weeks enhanced muscular strength and reduced muscular degeneration and fibrosis in mdx mice. Our findings provide preclinical proof-of-concept evidence that pharmacological activation of SERCA could be a promising therapeutic strategy for DMD. Moreover, CDN1163 improved muscular strength surprisingly in wild-type mice, which may pave the new way for the treatment of muscular dysfunction.

APA, Harvard, Vancouver, ISO, and other styles

46

Barton, Elisabeth R., Linda Morris, Antonio Musaro, Nadia Rosenthal, and H. Lee Sweeney. "Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice." Journal of Cell Biology 157, no. 1 (April 1, 2002): 137–48. http://dx.doi.org/10.1083/jcb.200108071.

Full text

Abstract:

Duchenne muscular dystrophy is an X-linked degenerative disorder of muscle caused by the absence of the protein dystrophin. A major consequence of muscular dystrophy is that the normal regenerative capacity of skeletal muscle cannot compensate for increased susceptibility to damage, leading to repetitive cycles of degeneration–regeneration and ultimately resulting in the replacement of muscle fibers with fibrotic tissue. 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. 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. Diaphragms of transgenic mdx:mIgf+/+ exhibited significant hypertrophy and hyperplasia at all ages observed. Furthermore, the IGF-I expression significantly reduced the amount of fibrosis normally observed in diaphragms from aged mdx mice. Decreased myonecrosis was also observed in diaphragms and quadriceps from mdx:mIgf+/+ mice when compared with age-matched mdx animals. Finally, signaling pathways associated with muscle regeneration and protection against apoptosis were significantly elevated. 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.

APA, Harvard, Vancouver, ISO, and other styles

47

Viola, Helena M., Stefan M. K. Davies, Aleksandra Filipovska, and Livia C. Hool. "L-type Ca2+ channel contributes to alterations in mitochondrial calcium handling in the mdx ventricular myocyte." American Journal of Physiology-Heart and Circulatory Physiology 304, no. 6 (March 15, 2013): H767—H775. http://dx.doi.org/10.1152/ajpheart.00700.2012.

Full text

Abstract:

The L-type Ca2+ channel is the main route for calcium entry into cardiac myocytes, and it is essential for contraction. Alterations in whole cell L-type Ca2+ channel current and Ca2+ homeostasis have been implicated in the development of cardiomyopathies. Cytoskeletal proteins can influence whole cell L-type Ca2+ current and mitochondrial function. Duchenne muscular dystrophy is a fatal X-linked disease that leads to progressive muscle weakness due to the absence of cytoskeletal protein dystrophin. This includes dilated cardiomyopathy, but the mechanisms are not well understood. We sought to identify the effect of alterations in whole cell L-type Ca2+ channel current on mitochondrial function in the murine model of Duchenne muscular dystrophy ( mdx). Activation of the L-type Ca2+ channel with the dihydropyridine agonist BayK(−) caused a significantly larger increase in cytosolic Ca2+ in mdx vs. wild-type ( wt) ventricular myocytes. Consistent with elevated cytosolic Ca2+, resting mitochondrial Ca2+, NADH, and mitochondrial superoxide were significantly greater in mdx vs. wt myocytes. Activation of the channel with BayK(−) caused a further increase in mitochondrial Ca2+, NADH, and superoxide in mdx myocytes. The ratios of the increases were similar to the ratios recorded in wt myocytes. In mitochondria isolated from 8-wk-old mdx hearts, respiration and mitochondrial electron transport chain complex activity were similar to mitochondria isolated from wt hearts. We conclude that mitochondria function at a higher level of resting calcium in the intact mdx myocyte and activation of the L-type Ca2+ channel contributes to alterations in calcium handling by the mitochondria. This perturbation may contribute to the development of cardiomyopathy.

APA, Harvard, Vancouver, ISO, and other styles

48

Lilling, Gilla, and Rivka Beitner. "Altered allosteric properties of cytoskeleton-bound phosphofructokinase in muscle from mice with X chromosome-linked muscular dystrophy (mdx)." Biochemical Medicine and Metabolic Biology 45, no. 3 (June 1991): 319–25. http://dx.doi.org/10.1016/0885-4505(91)90036-k.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Pelosi, Laura, Laura Forcina, Carmine Nicoletti, Bianca Maria Scicchitano, and Antonio Musarò. "Increased Circulating Levels of Interleukin-6 Induce Perturbation in Redox-Regulated Signaling Cascades in Muscle of Dystrophic Mice." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/1987218.

Full text

Abstract:

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease in which dystrophin gene is mutated, resulting in dysfunctional or absent dystrophin protein. The pathology of dystrophic muscle includes degeneration, necrosis with inflammatory cell invasion, regeneration, and fibrous and fatty changes. Nevertheless, the mechanisms by which the absence of dystrophin leads to muscle degeneration remain to be fully elucidated. An imbalance between oxidant and antioxidant systems has been proposed as a secondary effect of DMD. However, the significance and precise extent of the perturbation in redox signaling cascades is poorly understood. We report that mdx dystrophic mice are able to activate a compensatory antioxidant response at the presymptomatic stage of the disease. In contrast, increased circulating levels of IL-6 perturb the redox signaling cascade, even prior to the necrotic stage, leading to severe features and progressive nature of muscular dystrophy.

APA, Harvard, Vancouver, ISO, and other styles

50

Cui, Chang-Hao, Taro Uyama, Kenji Miyado, Masanori Terai, Satoru Kyo, Tohru Kiyono, and Akihiro Umezawa. "Menstrual Blood-derived Cells Confer Human Dystrophin Expression in the Murine Model of Duchenne Muscular Dystrophy via Cell Fusion and Myogenic Transdifferentiation." Molecular Biology of the Cell 18, no. 5 (May 2007): 1586–94. http://dx.doi.org/10.1091/mbc.e06-09-0872.

Full text

Abstract:

Duchenne muscular dystrophy (DMD), the most common lethal genetic disorder in children, is an X-linked recessive muscle disease characterized by the absence of dystrophin at the sarcolemma of muscle fibers. We examined a putative endometrial progenitor obtained from endometrial tissue samples to determine whether these cells repair muscular degeneration in a murine mdx model of DMD. Implanted cells conferred human dystrophin in degenerated muscle of immunodeficient mdx mice. We then examined menstrual blood–derived cells to determine whether primarily cultured nontransformed cells also repair dystrophied muscle. In vivo transfer of menstrual blood–derived cells into dystrophic muscles of immunodeficient mdx mice restored sarcolemmal expression of dystrophin. Labeling of implanted cells with enhanced green fluorescent protein and differential staining of human and murine nuclei suggest that human dystrophin expression is due to cell fusion between host myocytes and implanted cells. In vitro analysis revealed that endometrial progenitor cells and menstrual blood–derived cells can efficiently transdifferentiate into myoblasts/myocytes, fuse to C2C12 murine myoblasts by in vitro coculturing, and start to express dystrophin after fusion. These results demonstrate that the endometrial progenitor cells and menstrual blood–derived cells can transfer dystrophin into dystrophied myocytes through cell fusion and transdifferentiation in vitro and in vivo.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Muscular dystrophy X-linked mouse (mdx)'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles