Dp71 can restore the dystrophin-associated glycoprotein complex in muscle but fails to prevent dystrophy.
Two lines of transgenic mdx mice have been generated that express a 71 kD non-muscle isoform of dystrophin (Dp71) in skeletal muscle. This isoform contains the cysteine-rich and C-terminal domains of dystrophin, but lacks the N-terminal actin-binding and central spectrin-like repeat domains. Dp71 was associated with the sarcolemma membrane, where it restored normal expression and localization of all members of the dystrophin-associated glycoprotein complex. However, the skeletal muscle pathology of the transgenic mdx mice remained severe. These results indicate that the dystrophin C terminus cannot function independently to prevent dystrophic symptoms and confirms predictions based on patient data that both the N and C-terminal domains are required for normal dystrophin function.
Cox
G A
GA
Department of Human Genetics, University of Michigan Medical School, Ann Arbor 48109-0618.
Sunada
Y
Y
Campbell
K P
KP
Chamberlain
J S
JS
D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D016189:Dystrophin / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000517:prevention & control
D016189:Dystrophin; C085339:apo-dystrophin 1