Transgenic overexpression of dystroglycan does not inhibit muscular dystrophy in mdx mice.
Recently, there have been a number of studies demonstrating that overexpression of molecules in skeletal muscle can inhibit or ameliorate aspects of muscular dystrophy in the mdx mouse, a model for Duchenne muscular dystrophy. Several such studies involve molecules that increase the expression of dystroglycan, an important component of the dystrophin-glycoprotein complex. To test whether dystroglycan itself inhibits muscular dystrophy in mdx mice, we created dystroglycan transgenic mdx mice (DG/mdx). The alpha and beta chains of dystroglycan were highly overexpressed along the sarcolemmal membrane in most DG/mdx muscles. Increased dystroglycan expression, however, did not correlate with increased expression of utrophin or sarcoglycans, but rather caused their decreased expression. In addition, the percentage of centrally located myofiber nuclei and the level of serum creatine kinase activity were not decreased in DG/mdx mice relative to mdx animals. Therefore, dystroglycan overexpression does not cause the concomitant overexpression of a utrophin-glycoprotein complex in mdx muscles and has no effect on the development of muscle pathology associated with muscular dystrophy.
Hoyte
Kwame
K
Department of Neuroscience, Glycobiology Research and Training Center, University of California, San Diego, School of Medicine, La Jolla, California 92093-0691, USA.
Jayasinha
Vianney
V
Xia
Bing
B
Martin
Paul T
PT
D000818:Animals; D015153:Blotting, Western; D003402:Creatine Kinase / Q000097:blood; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D049030:Dystroglycans; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D012508:Sarcolemma / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D049411:Utrophin
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C483600:Utrn protein, mouse; D049411:Utrophin; D049030:Dystroglycans; D003402:Creatine Kinase