Experimental regeneration in canine muscular dystrophy--1. Immunocytochemical evaluation of dystrophin and beta-spectrin expression.
The expression of dystrophin and beta-spectrin was examined from 1 to 56 days in regenerating muscle fibres in normal and dystrophic dogs, following necrosis induced by the venom of Notechis scutatis. Normal and dystrophic dog muscle regenerated at an equal rate and new myotubes were present in both at the periphery of necrotic fibres by 3 days. In normal dogs dystrophin was detected in the sarcoplasm of the regenerating fibres by 3 days and was localized to the plasma membrane by 4 days. The localization of dystrophin is independent of beta-spectrin and was detected before beta-spectrin, which was not observed until 5-6 days. Normal peripheral labelling of both was restored by 14 days in normal dogs. Normal beta-spectrin labelling of regenerating dystrophic fibres was also restored by 14 days and is not dependent on the presence of dystrophin in dystrophic dogs. A proportion of regenerating fibres in normal and dystrophic dogs showed weak immunolabelling of beta-spectrin prior to 14 days. This is a feature of immature muscle fibres. Antibodies to different domains of dystrophin bound to the periphery and sarcoplasm of regenerating fibres in dystrophic dogs, particularly during the first 7 days of regeneration, but the fluorescence was less intense than in normal dogs. Weak labelling with antibodies corresponding to the C-terminus of the rod domain of dystrophin persisted on dystrophic regenerating fibres up to 21 days. This may relate to developmental isoforms of dystrophin.
Sewry
C A
CA
Department of Paediatrics and Neonatal Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Wilson
L A
LA
Dux
L
L
Dubowitz
V
V
Cooper
B J
BJ
D000818:Animals; D004283:Dog Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004285:Dogs; D016189:Dystrophin / Q000096:biosynthesis*; D004546:Elapid Venoms; D007150:Immunohistochemistry; D009132:Muscles / Q000473:pathology / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009336:Necrosis; D012038:Regeneration / Q000502:physiology*; D013049:Spectrin / Q000096:biosynthesis*
D016189:Dystrophin; D004546:Elapid Venoms; D013049:Spectrin