Expression of utrophin (dystrophin-related protein) during regeneration and maturation of skeletal muscle in canine X-linked muscular dystrophy.
The regulation of utrophin, the autosomal homologue of dystrophin, has been studied in the canine X-linked model of Duchenne muscular dystrophy. Dystrophic muscle has been shown to exhibit abnormal sarcolemmal expression of utrophin, in addition to the normal expression at the neuromuscular junction, in peripheral nerves, vascular tissues and regenerating fibres. To establish whether this abnormal presence of utrophin in dystrophic muscle is a consequence of continued expression following regeneration, or is attributable to a disease related up-regulation, the expression of utrophin was compared immunocytochemically with that of dystrophin, beta-spectrin and neonatal myosin in regenerating normal and dystrophic canine muscle, following necrosis induced by the injection of venom from the snake Notechis iscutatis. In normal regenerating muscle, sarcolemmal utrophin and dystrophin were detected concomitantly from 2-3 d post-injection, prior to the expression of beta-spectrin. Down-regulation of utrophin was apparent in some fibres from 7 d, and it was no longer present on the extra-junctional sarcolemma by 14 d. Neonatal myosin was still present in all fibres at this stage, but dystrophin and beta-spectrin had been fully restored. In dystrophic regenerating muscle, down-regulation of utrophin occurred from 7 d, although it persisted on some fibres until 28 d, longer than in normal muscle. At 42 d, however, utrophin in dystrophic muscle was only detected in a population of small fibres thought to represent a second cycle of regeneration, with no immunolabelling of mature fibres.(ABSTRACT TRUNCATED AT 250 WORDS)
Wilson
L A
LA
Department of Paediatrics and Neonatal Medicine, Royal Postgraduate Medical School, London, UK.
Cooper
B J
BJ
Dux
L
L
Dubowitz
V
V
Sewry
C A
CA
D000818:Animals; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D004285:Dogs; D008040:Genetic Linkage; D007150:Immunohistochemistry; D008565:Membrane Proteins; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009218:Myosins / Q000096:biosynthesis; D009336:Necrosis / Q000473:pathology; D012038:Regeneration; D013049:Spectrin / Q000096:biosynthesis; D015854:Up-Regulation / Q000502:physiology; D049411:Utrophin; D014960:X Chromosome
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D049411:Utrophin; D013049:Spectrin; D009218:Myosins