Sarcospan Regulates Cardiac Isoproterenol Response and Prevents Duchenne Muscular Dystrophy-Associated Cardiomyopathy.

BackgroundDuchenne muscular dystrophy is a fatal cardiac and skeletal muscle disease resulting from mutations in the dystrophin gene. We have previously demonstrated that a dystrophin-associated protein, sarcospan (SSPN), ameliorated Duchenne muscular dystrophy skeletal muscle degeneration by activating compensatory pathways that regulate muscle cell adhesion (laminin-binding) to the extracellular matrix. Conversely, loss of SSPN destabilized skeletal muscle adhesion, hampered muscle regeneration, and reduced force properties. Given the importance of SSPN to skeletal muscle, we investigated the consequences of SSPN ablation in cardiac muscle and determined whether overexpression of SSPN into mdx mice ameliorates cardiac disease symptoms associated with Duchenne muscular dystrophy cardiomyopathy.Methods and resultsSSPN-null mice exhibited cardiac enlargement, exacerbated cardiomyocyte hypertrophy, and increased fibrosis in response to β-adrenergic challenge (isoproterenol; 0.8 mg/day per 2 weeks). Biochemical analysis of SSPN-null cardiac muscle revealed reduced sarcolemma localization of many proteins with a known role in cardiomyopathy pathogenesis: dystrophin, the sarcoglycans (α-, δ-, and γ-subunits), and β1D integrin. Transgenic overexpression of SSPN in Duchenne muscular dystrophy mice (mdx(TG)) improved cardiomyofiber cell adhesion, sarcolemma integrity, cardiac functional parameters, as well as increased expression of compensatory transmembrane proteins that mediate attachment to the extracellular matrix.ConclusionsSSPN regulates sarcolemmal expression of laminin-binding complexes that are critical to cardiac muscle function and protects against transient and chronic injury, including inherited cardiomyopathy

The quality of life in boys with Duchenne muscular dystrophy

We conducted a study to evaluate the quality of life in boys with Duchenne muscular dystrophy aged 8–18 years, compared with that in matched healthy controls. A total of 85 boys with Duchenne muscular dystrophy aged 8–18 years and 136 age, sex and living place matched healthy controls were included in this study. Patients and one of their parents separately completed the 27-item Persian version of KIDSCREEN questionnaire (child and adolescent version and parent version). From the children's perspective, the quality of life in patients was found to be lower in two subclasses: “physical activities and health” (p < 0.001) and “friends” (p = 0.005). Parental estimation of their sick child's quality of life was significantly lower than children's own assessment in two subclasses: “physical activities and health” (p < 0.001) and “general mood and feelings” (p < 0.001). Our results indicate that boys with Duchenne muscular dystrophy have quite a satisfactory quality of life. A happier and more hopeful life can be promoted through increasing social support and improving the parental knowledge regarding their child's more positive life perspective. © 2016 Elsevier B.V

Cognitive Function and Quality of Life of Muscular Dystrophy

Duchenne muscular dystrophy and myotonic dystrophy are genetic, progressive muscle diseases. These muscular dystrophies, which are currently incurable, cause muscle wasting or muscle weakness and decrease patients’ quality of life. In addition to muscular impairments, cognitive impairments are also reported in both Duchenne muscular dystrophy and myotonic dystrophy. Cognitive impairments in each type of muscular dystrophy are different and closely related to psychosocial variables and the quality of life of the patients. We reviewed the features of cognitive functions in each type of muscular dystrophy and their correlations with the quality of life of patients. Based on the findings, we have suggested effective interventions for improving the quality of life of muscular dystrophy patients

Circulating small RNA signatures differentiate accurately the subtypes of muscular dystrophies: small-RNA next-generation sequencing analytics and functional insights

Muscular dystrophies are a group of rare and severe inherited disorders mainly affecting the muscle tissue. Duchene Muscular Dystrophy, Myotonic Dystrophy types 1 and 2, Limb Girdle Muscular Dystrophy and Facioscapulohumeral Muscular Dystrophy are some of the members of this family of disorders. In addition to the current diagnostic tools, there is an increasing interest for the development of novel non-invasive biomarkers for the diagnosis and monitoring of these diseases. miRNAs are small RNA molecules characterized by high stability in blood thus making them ideal biomarker candidates for various diseases. In this study, we present the first genome-wide next-generation small RNA sequencing in serum samples of five different types of muscular dystrophy patients and healthy individuals. We identified many small RNAs including miRNAs, lncRNAs, tRNAs, snoRNAs and snRNAs, that differentially discriminate the muscular dystrophy patients from the healthy individuals. Further analysis of the identified miRNAs showed that some miRNAs can distinguish the muscular dystrophy patients from controls and other miRNAs are specific to the type of muscular dystrophy. Bioinformatics analysis of the target genes for the most significant miRNAs and the biological role of these genes revealed different pathways that the dysregulated miRNAs are involved in each type of muscular dystrophy investigated. In conclusion, this study shows unique signatures of small RNAs circulating in five types of muscular dystrophy patients and provides a useful resource for future studies for the development of miRNA biomarkers in muscular dystrophies and for their involvement in the pathogenesis of the disorders

The Muscular Dystrophy Association

Muscular dystrophy (MD) is a social problem because the people affected by it do not get to live a normal life.https://digitalscholarship.unlv.edu/educ_sys_202/1016/thumbnail.jp

An uncommon variant of rare type of muscular dystrophy

The muscular dystrophies are a group of hereditary degenerative diseases characterised by progressive myopathy. Emery-Dreifuss muscular dystrophy (EDMD) is a rare genetically heterogenous type of muscular dystrophy characterized by early contractures (especially in the neck, elbows and ankles), slowly progressing muscle weakness more prominent in humeroperoneal region, onset in early childhood and cardiac problems. Emery-Dreifuss muscular dystrophy is commonly inherited in an X linked recessive pattern and rarely autosomal dominant inheritance or autosomal recessive fashion. Here we report a case of autosomal recessive type of Emery-Dreifuss muscular dystrophy from our hospital

Cytokines and chemokines as regulators of skeletal muscle inflammation: presenting the case of Duchenne muscular dystrophy

Duchenne muscular dystrophy is a severe inherited muscle disease that affects 1 in 3500 boys worldwide. Infiltration of skeletal muscle by inflammatory cells is an important facet of disease pathophysiology and is strongly associated with disease severity in the individual patient. In the chronic inflammation that characterizes Duchenne muscle, cytokines and chemokines are considered essential activators and recruiters of inflammatory cells. In addition, they provide potential beneficiary effects on muscle fiber damage control and tissue regeneration. In this review, current knowledge of cytokine and chemokine expression in Duchenne muscular dystrophy and its relevant animal disease models is listed, and implications for future therapeutic avenues are discussed

The genetics of the muscular dystrophies

When one mentions muscular dystrophy, the mental picture that emerges is that of Duchene Muscular Dystrophy (DMD). In reality, the term muscular dystrophy refers to around six, heterogenous groups of inherited disorders characterised by progressive muscle wasting and weakness. The common feature of all the dystrophies is the histological picture of muscle biopsy with the typical signs of muscle fibre variation, muscle necrosis and increased fat and connective tissues.peer-reviewe

Abnormality of water homeostasis of Muscular dystrophic chicken

The muscular dystrophy chicken has been studying as model animal of muscular dystrophy for more than 50 years. Recently, the mutation of WW domain containing E3 ubiquitin protein ligase 1 (WWP1) gene has been identified as a responsible for muscular dystrophy chicken. We observed that muscular dystrophy chicken not only showed the degeneration of skeletal muscles but also produced watery feces. Therefore, we examined the possibility of abnormalities in water metabolism of muscular dystrophy chicken. We first analyzed plasma osmolality and gene expression of aquaporin 2 (AQP2), AQP3 and alpha subunit of the amiloride-sensitive epithelial sodium channel (αENaC) in muscular dystrophy chicken and White Leghorn chicken under normal physiological conditions at five-week old. Subsequently, we analyzed these same parameters after one-day water-deprivation. The main findings of our study are that: I) the plasma osmolality was significantly higher in muscular dystrophic chicken than in White Leghorn; II) kidney αENaC mRNA expression was significantly lower in muscular dystrophic chicken than in White Leghorn; III) AQP2 and AQP3 mRNA expressions in muscular dystrophic chicken were similar in White Leghorn. We suggest that the mutation of WWP1 may cause the abnormality of sodium absorption, and thus muscular dystrophic chicken become hypernatremic

Characteristics and Effects of Muscular Dystrophy in Broiler Chickens

Muscular dystrophy is very common among broilers, which are chickens raised specifically for meat production. When dystrophic chickens are mated, or when normal and dystrophic chickens are mated, it is very likely that at least fifty percent of the clutch will end up with muscular dystrophy since it is inherited as a co-dominant disorder (Fujiwara et al., 2009). For my study, eggs were obtained from a local farm, and allowed to hatch. Among these hatchings were chicks who exhibited some traits of muscular dystrophy. It is possible that the parents of the seemingly dystrophic chicks may carry the mutated WWP1 allele which would cause the chicks to exhibit these traits. Because chickens are useful animal models of disease, it is important to try to understand the mutations in the WWP1 gene so we can see exactly how it affects the ubiquitin-ligase pathway, and how we can work to reverse the mutations to eliminate the disease all together. Understanding the disease in chickens may help us to further understand muscular dystrophy in humans as well. By taking feathers from the potentially dystrophic chicks and their parents, phenotypic characterization of these chicks was done to confirm diagnosis of muscular dystrophy. Further DNA sequencing for the WWP1 mutation associated with muscular dystrophy (Hirokazu et al., 2008) was performed to determine whether these chicks had the previously characterized mutation for muscular dystrophy in this gene