What has the mdx mouse model of duchenne muscular dystrophy contributed to our understanding of this disease?

Manning, Jennifer; O’Malley, Dervla

doi:10.1007/s10974-015-9406-4

Cited by 63 publications

(59 citation statements)

References 157 publications

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“…Scale bar 50 lm (4 mice and 6 sections were analyzed per animal) In addition to apoptotic cell death, skeletal muscles of mdx mice and patients with DMD present necrosis reflected by high circulating levels of serum creatine kinase (CK) [36,37]. As described previously [38], CK activity in serum samples of mdx mice was *30 times higher than in serum of control animals (Fig. 9a).…”

Section: The Absence Of Cx43 and Cx45 Abrogates Nf-jb Activation And mentioning

confidence: 52%

Fast skeletal myofibers of mdx mouse, model of Duchenne muscular dystrophy, express connexin hemichannels that lead to apoptosis

Luis

Puebla

Cisterna

et al. 2016

Cell. Mol. Life Sci.

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Skeletal muscles of patients with Duchenne muscular dystrophy (DMD) show numerous alterations including inflammation, apoptosis, and necrosis of myofibers. However, the molecular mechanism that explains these changes remains largely unknown. Here, the involvement of hemichannels formed by connexins (Cx HCs) was evaluated in skeletal muscle of mdx mouse model of DMD. Fast myofibers of mdx mice were found to express three connexins (39, 43 and 45) and high sarcolemma permeability, which was absent in myofibers of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice (deficient in skeletal muscle Cx43/Cx45 expression). These myofibers did not show elevated basal intracellular free Ca(2+) levels, immunoreactivity to phosphorylated p65 (active NF-κB), eNOS and annexin V/active Caspase 3 (marker of apoptosis) but presented dystrophin immunoreactivity. Moreover, muscles of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice exhibited partial decrease of necrotic features (big cells and high creatine kinase levels). Accordingly, these muscles showed similar macrophage infiltration as control mdx muscles. Nonetheless, the hanging test performance of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice was significantly better than that of control mdx Cx43(fl/fl)Cx45(fl/fl) mice. All three Cxs found in skeletal muscles of mdx mice were also detected in fast myofibers of biopsy specimens from patients with muscular dystrophy. Thus, reduction of Cx expression and/or function of Cx HCs may be potential therapeutic approaches to abrogate myofiber apoptosis in DMD.

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Section: The Absence Of Cx43 and Cx45 Abrogates Nf-jb Activation And mentioning

confidence: 52%

Fast skeletal myofibers of mdx mouse, model of Duchenne muscular dystrophy, express connexin hemichannels that lead to apoptosis

Luis

Puebla

Cisterna

et al. 2016

Cell. Mol. Life Sci.

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“…DMD has been studied extensively through one model system in particular: the mdx mouse [reviewed in (412)]. The mdx mouse arose from a spontaneous mutation in the C57BL/10 strain and has a phenotype comparable to human DMD (82).…”

Section: The Costamere: Protects Against Mechanical Stress and Is An mentioning

confidence: 99%

Overview of the Muscle Cytoskeleton

Henderson

Gomez

Novak

et al. 2017

Comprehensive Physiology

226

193

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Cardiac and skeletal striated muscles are intricately designed machines responsible for muscle contraction. Coordination of the basic contractile unit, the sarcomere, and the complex cytoskeletal networks are critical for contractile activity. The sarcomere is comprised of precisely organized individual filament systems that include thin (actin), thick (myosin), titin, and nebulin. Connecting the sarcomere to other organelles (e.g., mitochondria and nucleus) and serving as the scaffold to maintain cellular integrity are the intermediate filaments. The costamere, on the other hand, tethers the sarcomere to the cell membrane. Unique structures like the intercalated disc in cardiac muscle and the myotendinous junction in skeletal muscle help synchronize and transmit force. Intense investigation has been done on many of the proteins that make up these cytoskeletal assemblies. Yet the details of their function and how they interconnect have just started to be elucidated. A vast number of human myopathies are contributed to mutations in muscle proteins; thus understanding their basic function provides a mechanistic understanding of muscle disorders. In this review, we highlight the components of striated muscle with respect to their interactions, signaling pathways, functions, and connections to disease.

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“…To assess the effects of growth hormone on bone and muscle, this study used the most widely used animal model of DMD, the mdx mouse, to examine the effects of daily growth hormone administration in the absence and presence of glucocorticoid treatment. We used young, 5‐ to 10‐week‐old male mdx mice that are undergoing rapid bone growth, equivalent to that observed in boys when glucocorticoid treatment is initiated.…”

Section: Introductionmentioning

confidence: 99%

“…We used young, 5‐ to 10‐week‐old male mdx mice that are undergoing rapid bone growth, equivalent to that observed in boys when glucocorticoid treatment is initiated. Although mdx mice have no functional dystrophin protein, they show a milder form of muscular dystrophy than DMD patients, likely because of the upregulation of utrophin expression and persistent muscle fiber regeneration in the mice . Nevertheless, mdx mice show significant muscle weakness at young ages that responds positively to glucocorticoids .…”

Section: Introductionmentioning

confidence: 99%

Growth Hormone Increases Bone Toughness and Decreases Muscle Inflammation in Glucocorticoid-Treated Mdx Mice, Model of Duchenne Muscular Dystrophy

Yoon

Grynpas

Mitchell

2019

Journal of Bone and Mineral Research

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The absence of functional dystrophin with mutations of the dystrophin‐encoding gene in Duchenne muscular dystrophy (DMD) results in muscle inflammation and degeneration, as well as bone fragility. Long‐term glucocorticoid therapy delays the muscular disease progression but suppresses growth hormone secretion, resulting in short stature and further deleterious effects on bone strength. This study evaluated the therapeutic potential of daily growth hormone therapy in growing mdx mice as a model of DMD. Growth hormone treatment on its own or in combination with glucocorticoids significantly improved muscle histology and function and decreased markers of inflammation in mdx mice. Glucocorticoid treatment thinned cortical bone and decreased bone strength and toughness. Despite the minimal effects of growth hormone on bone microarchitecture, it significantly improved biomechanical properties of femurs and vertebrae, even in the presence of glucocorticoid treatment. Together these studies suggest that the use of growth hormone in DMD should be considered for improvements to muscle and bone health. © 2019 American Society for Bone and Mineral Research.

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What has the mdx mouse model of duchenne muscular dystrophy contributed to our understanding of this disease?

Cited by 63 publications

References 157 publications

Fast skeletal myofibers of mdx mouse, model of Duchenne muscular dystrophy, express connexin hemichannels that lead to apoptosis

Fast skeletal myofibers of mdx mouse, model of Duchenne muscular dystrophy, express connexin hemichannels that lead to apoptosis

Overview of the Muscle Cytoskeleton

Growth Hormone Increases Bone Toughness and Decreases Muscle Inflammation in Glucocorticoid-Treated Mdx Mice, Model of Duchenne Muscular Dystrophy

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