Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle

Nature ◽  
1992 ◽  
Vol 360 (6404) ◽  
pp. 588-591 ◽  
Author(s):  
Kiichiro Matsumura ◽  
James M. Ervasti ◽  
Kay Ohlendieck ◽  
Steven D. Kahl ◽  
Kevin P. Campbell
Keyword(s):  
Mdx Mouse ◽  
Related Protein ◽  
Mouse Muscle ◽  
Associated Proteins

scholarly journals Dystrophin-associated proteins are greatly reduced in skeletal muscle from mdx mice.

1991 ◽  
Vol 115 (6) ◽  
pp. 1685-1694 ◽  
Author(s):  
K Ohlendieck ◽  
K P Campbell
Keyword(s):  
Skeletal Muscle ◽  
Immunoblot Analysis ◽  
Protein Product ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Normal Density ◽  
Mouse Muscle ◽  
Glycoprotein Complex ◽  
Associated Proteins ◽  
Dy Mouse

Dystrophin, the protein product of the human Duchenne muscular dystrophy gene, exists in skeletal muscle as a large oligomeric complex that contains four glycoproteins of 156, 50, 43, and 35 kD and a protein of 59 kD. Here, we investigated the relative abundance of each of the components of the dystrophin-glycoprotein complex in skeletal muscle from normal and mdx mice, which are missing dystrophin. Immunoblot analysis using total muscle membranes from control and mdx mice of ages 1 d to 30 wk found that all of the dystrophin-associated proteins were greatly reduced (80-90%) in mdx mouse skeletal muscle. The specificity of the loss of the dystrophin-associated glycoproteins was demonstrated by the finding that the major glycoprotein composition of skeletal muscle membranes from normal and mdx mice was identical. Furthermore, skeletal muscle membranes from the dystrophic dy/dy mouse exhibited a normal density of dystrophin and dystrophin-associated proteins. Immunofluorescence microscopy confirmed the results from the immunoblot analysis and showed a drastically reduced density of dystrophin-associated proteins in mdx muscle cryosections compared with normal and dy/dy mouse muscle. Therefore, our results demonstrate that all of the dystrophin-associated proteins are significantly reduced in mdx skeletal muscle and suggest that the loss of dystrophin-associated proteins is due to the absence of dystrophin and not due to secondary effects of muscle fiber degradation.

Acute pathophysiological effects of muscle-expressed Dp71 transgene on normal and dystrophic mouse muscle

2003 ◽  
Vol 95 (5) ◽  
pp. 1861-1866 ◽  
Author(s):  
Sascha Wieneke ◽  
Peter Heimann ◽  
Sigalit Leibovitz ◽  
Uri Nudel ◽  
Harald Jockusch
Keyword(s):  
Muscular Dystrophy ◽  
Dystrophin Gene ◽  
Force Generation ◽  
Mdx Mouse ◽  
Mouse Muscle ◽  
Tetanic Force ◽  
Dystrophin Deficiency ◽  
Associated Proteins ◽  
Isometric Twitch ◽  
Tetanic Tension

products of the dystrophin gene range from the 427-kDa full-length dystrophin to the 70.8-kDa Dp71. Dp427 is expressed in skeletal muscle, where it links the actin cytoskeleton with the extracellular matrix via a complex of dystrophin-associated proteins (DAPs). Dystrophin deficiency disrupts the DAP complex and causes muscular dystrophy in humans and the mdx mouse. Dp71, the major nonmuscle product, consists of the COOH-terminal part of dystrophin, including the binding site for the DAP complex but lacks binding sites for microfilaments. Dp71 transgene (Dp71tg) expressed in mdx muscle restores the DAP complex but does not prevent muscle degeneration. In wild-type (WT) mouse muscle, Dp71tg causes a mild muscular dystrophy. In this study, we tested, using isolated extensor digitorum longus muscles, whether Dp71tg exerts acute influences on force generation and sarcolemmal stress resistance. In WT muscles, there was no effect on isometric twitch and tetanic force generation, but with a cytomegalovirus promotor-driven transgene, contraction with stretch led to sarcolemmal ruptures and irreversible loss of tension. In MDX muscle, Dp71tg reduced twitch and tetanic tension but did not aggravate sarcolemmal fragility. The adverse effects of Dp71 in muscle are probably due to its competition with dystrophin and utrophin (in MDX muscle) for binding to the DAP complex.

scholarly journals Investigation of the effect of taurine supplementation on muscle taurine content in the mdx mouse model of Duchenne muscular dystrophy using chemically specific synchrotron imaging

The Analyst ◽  
2020 ◽  
Vol 145 (22) ◽  
pp. 7242-7251
Author(s):  
Jessica R. Terrill ◽  
Samuel M. Webb ◽  
Peter G. Arthur ◽  
Mark J. Hackett
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Muscle Tissue ◽  
Mdx Mouse ◽  
Taurine Supplementation ◽  
Mouse Muscle ◽  
Synchrotron Imaging

Sulfur K-edge XANES was used to quantify changes in the taurine content of mouse muscle tissue in a model of muscular dystrophy. The changes could be associated with markers of disease pathology that were revealed by classical H&E histology.

Regenerated mdx mouse skeletal muscle shows differential mRNA expression

2002 ◽  
Vol 93 (2) ◽  
pp. 537-545 ◽  
Author(s):  
B. S. Tseng ◽  
P. Zhao ◽  
J. S. Pattison ◽  
S. E. Gordon ◽  
J. A. Granchelli ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein A ◽  
Mdx Mouse ◽  
Related Protein ◽  
Muscle Involvement ◽  
Oxidative And Glycolytic Enzymes ◽  
Salvage Pathways ◽  
Mast Cell Chymase ◽  
Dystrophin Protein ◽  
Differential Mrna Expression

Despite over 3,000 articles published on dystrophin in the last 15 years, the reasons underlying the progression of the human disease, differential muscle involvement, and disparate phenotypes in different species are not understood. The present experiment employed a screen of 12,488 mRNAs in 16-wk-old mouse mdx muscle at a time when the skeletal muscle is avoiding severe dystrophic pathophysiology, despite the absence of a functional dystrophin protein. A number of transcripts whose levels differed between the mdx and human Duchenne muscular dystrophy were noted. A fourfold decrease in myostatin mRNA in the mdx muscle was noted. Differential upregulation of actin-related protein 2/3 (subunit 4), β-thymosin, calponin, mast cell chymase, and guanidinoacetate methyltransferase mRNA in the more benign mdx was also observed. Transcripts for oxidative and glycolytic enzymes in mdx muscle were not downregulated. These discrepancies could provide candidates for salvage pathways that maintain skeletal muscle integrity in the absence of a functional dystrophin protein in mdx skeletal muscle.

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