scholarly journals Progressive myopathy in an inducible mouse model of oculopharyngeal muscular dystrophy

2012 ◽  
Vol 45 (1) ◽  
pp. 539-546 ◽  
Author(s):  
Ami Mankodi ◽  
Thurman M. Wheeler ◽  
Reena Shetty ◽  
Kelly M. Salceies ◽  
Mark W. Becher ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Mouse Model ◽  
Oculopharyngeal Muscular Dystrophy

scholarly journals Molecular and phenotypic characterization of a mouse model of oculopharyngeal muscular dystrophy reveals severe muscular atrophy restricted to fast glycolytic fibres

2010 ◽  
Vol 19 (11) ◽  
pp. 2191-2207 ◽  
Author(s):  
Capucine Trollet ◽  
Seyed Yahya Anvar ◽  
Andrea Venema ◽  
Iain P. Hargreaves ◽  
Keith Foster ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Mouse Model ◽  
Muscular Atrophy ◽  
Phenotypic Characterization ◽  
Oculopharyngeal Muscular Dystrophy

Cystamine Suppresses Polyalanine Toxicity in a Mouse Model of Oculopharyngeal Muscular Dystrophy

2010 ◽  
Vol 2 (34) ◽  
pp. 34ra40-34ra40 ◽  
Author(s):  
J. E. Davies ◽  
C. Rose ◽  
S. Sarkar ◽  
D. C. Rubinsztein
Keyword(s):  
Muscular Dystrophy ◽  
Mouse Model ◽  
Oculopharyngeal Muscular Dystrophy

scholarly journals 500. Gene Therapy Rescues Disease Phenotype in the Oculopharyngeal Muscular Dystrophy Mouse Model

2016 ◽  
Vol 24 ◽  
pp. S199
Author(s):  
George Dickson ◽  
Alberto Malerba ◽  
Pierre Klein ◽  
Susan Jarmin ◽  
Houria Bachtarzi ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Oculopharyngeal Muscular Dystrophy ◽  
Disease Phenotype

scholarly journals Guanabenz treatment improves Oculopharyngeal muscular dystrophy phenotype

2018 ◽  
Author(s):  
Alberto Malerba ◽  
Fanny Roth ◽  
Pradeep Harish ◽  
Jamila Dhiab ◽  
Ngoc Lu-Nguyen ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Mouse Model ◽  
Genetic Disease ◽  
Late Onset ◽  
Oculopharyngeal Muscular Dystrophy ◽  
Systemic Delivery ◽  
Active Constituent ◽  
Eukaryotic Translation ◽  
Pharyngeal Muscles ◽  
The Unfolded Protein Response

AbstractOculopharyngeal muscular dystrophy (OPMD) is a rare late onset genetic disease affecting most profoundly eyelid and pharyngeal muscles, leading respectively to ptosis and dysphagia, and proximal limb muscles at later stages. A short abnormal (GCG) triplet expansion in the polyA– binding protein nuclear 1 (PABPN1) gene leads to PABPN1-containing aggregates in the muscles of OPMD patients. It is commonly accepted that aggregates themselves, the aggregation process and/or the early oligomeric species of PABPN1 are toxic in OPMD. Decreasing PABPN1 aggregate load in animal models of OPMD ameliorates the muscle phenotype. In order to identify a potential therapeutic molecule that would prevent and reduce aggregates, we tested guanabenz acetate (GA), an FDA-approved antihypertensive drug, in OPMD cells as well as in the A17 OPMD mouse model. We demonstrate that treating mice with GA reduces the size and number of nuclear aggregates, improves muscle force, protects myofibres from the pathology-derived turnover and decreases fibrosis. GA is known to target various cell processes, including the unfolded protein response (UPR), which acts to attenuate endoplasmic reticulum (ER) stress. Here we used a cellular model of OPMD to demonstrate that GA increases both the phosphorylation of the eukaryotic translation initiator factor 2α subunit (eIF2α) and the splicing of Xbp1, key components of the UPR. Altogether these data suggest that modulation of protein folding regulation can be beneficial for OPMD and support the further development of guanabenz or its derivatives for treatment of OPMD in humans.Significance StatementOculopharyngeal muscular dystrophy (OPMD) is a rare late onset incurable genetic disease characterized by the formation of insoluble aggregates in skeletal muscles. It has been shown that the reduction of aggregates correlates with an improvement of the disease. Here we used a mouse model of OPMD to show that Guanabenz acetate, the active constituent of a marketed but recently discontinued drug for hypertension, decreases the number and the size of aggregates after systemic delivery and improves many aspects of the disease. We also describe experimental evidences explaining the mechanism behind the efficacy of such compound for OPMD.

Regenerating myofibers in tibialis anterior muscles of young ‘MDX’ mice

1987 ◽  
Vol 45 ◽  
pp. 726-727
Author(s):  
H. D. Geissinge ◽  
L.D. Rhodes
Keyword(s):  
Muscular Dystrophy ◽  
Mouse Model ◽  
Tibialis Anterior ◽  
Physiological Activity ◽  
Mdx Mice ◽  
Mode Of Inheritance

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.

Unusual triplet expansion associated with neurogenic changes in a family with oculopharyngeal muscular dystrophy

2001 ◽  
Vol 21 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Ralf Schober ◽  
Wolfram Kress ◽  
Friedrich Grahmann ◽  
Steffen Kellermann ◽  
Petra Baum ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Oculopharyngeal Muscular Dystrophy ◽  
Triplet Expansion
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