Expression of utrophin (dystrophin-related protein) during regeneration and maturation of skeletal muscle in canine X-linked muscular dystrophy

L. A. Wilson, B. J. Cooper, L. Dux, V. Dubowitz, C. A. Sewry

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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, β-spectrin and neonatal myosin in regenerating normal and dystrophic canine muscle, following necrosis induced by the injection of venom from the snake Notechis scutatis. In normal regenerating muscle, sarcolemmal utrophin and dystrophin were detected concomitantly from 2-3 d post-injection, prior to the expression of β-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 β-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. The results show that most utrophin is down-regulated in regenerating dystrophic fibres, prior to neonatal myosin, thus abnormal sarcolemmal expression of utrophin in dystrophic muscle is unlikely to be a continuation of the maturational process. Persistence of both utrophin and neonatal myosin, however, suggest a delay in the maturation of dystrophic muscle. In addition, a second cycle of degeneration and regeneration in dystrophic muscle does not occur whilst utrophin is still present, suggesting it may have a protective role against fibre damage and necrosis.

Original languageEnglish
Pages (from-to)359-367
Number of pages9
JournalNeuropathology and Applied Neurobiology
Volume20
Issue number4
Publication statusPublished - 1994

Fingerprint

Utrophin
Muscular Dystrophies
Canidae
Regeneration
Skeletal Muscle
Muscles
Dystrophin
Myosins
Spectrin
Necrosis
Down-Regulation
Nerve Tissue
Sarcolemma
Snake Venoms
Injections
Duchenne Muscular Dystrophy
Neuromuscular Junction
Peripheral Nerves

Keywords

  • Duchenne muscular dystrophy
  • Dystrophic dog
  • Dystrophin
  • Dystrophin-related protein
  • Regeneration
  • Skeletal muscle
  • Utrophin

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Expression of utrophin (dystrophin-related protein) during regeneration and maturation of skeletal muscle in canine X-linked muscular dystrophy. / Wilson, L. A.; Cooper, B. J.; Dux, L.; Dubowitz, V.; Sewry, C. A.

In: Neuropathology and Applied Neurobiology, Vol. 20, No. 4, 1994, p. 359-367.

Research output: Contribution to journalArticle

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abstract = "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, β-spectrin and neonatal myosin in regenerating normal and dystrophic canine muscle, following necrosis induced by the injection of venom from the snake Notechis scutatis. In normal regenerating muscle, sarcolemmal utrophin and dystrophin were detected concomitantly from 2-3 d post-injection, prior to the expression of β-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 β-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. The results show that most utrophin is down-regulated in regenerating dystrophic fibres, prior to neonatal myosin, thus abnormal sarcolemmal expression of utrophin in dystrophic muscle is unlikely to be a continuation of the maturational process. Persistence of both utrophin and neonatal myosin, however, suggest a delay in the maturation of dystrophic muscle. In addition, a second cycle of degeneration and regeneration in dystrophic muscle does not occur whilst utrophin is still present, suggesting it may have a protective role against fibre damage and necrosis.",
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AU - Dubowitz, V.

AU - Sewry, C. A.

PY - 1994

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N2 - 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, β-spectrin and neonatal myosin in regenerating normal and dystrophic canine muscle, following necrosis induced by the injection of venom from the snake Notechis scutatis. In normal regenerating muscle, sarcolemmal utrophin and dystrophin were detected concomitantly from 2-3 d post-injection, prior to the expression of β-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 β-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. The results show that most utrophin is down-regulated in regenerating dystrophic fibres, prior to neonatal myosin, thus abnormal sarcolemmal expression of utrophin in dystrophic muscle is unlikely to be a continuation of the maturational process. Persistence of both utrophin and neonatal myosin, however, suggest a delay in the maturation of dystrophic muscle. In addition, a second cycle of degeneration and regeneration in dystrophic muscle does not occur whilst utrophin is still present, suggesting it may have a protective role against fibre damage and necrosis.

AB - 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, β-spectrin and neonatal myosin in regenerating normal and dystrophic canine muscle, following necrosis induced by the injection of venom from the snake Notechis scutatis. In normal regenerating muscle, sarcolemmal utrophin and dystrophin were detected concomitantly from 2-3 d post-injection, prior to the expression of β-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 β-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. The results show that most utrophin is down-regulated in regenerating dystrophic fibres, prior to neonatal myosin, thus abnormal sarcolemmal expression of utrophin in dystrophic muscle is unlikely to be a continuation of the maturational process. Persistence of both utrophin and neonatal myosin, however, suggest a delay in the maturation of dystrophic muscle. In addition, a second cycle of degeneration and regeneration in dystrophic muscle does not occur whilst utrophin is still present, suggesting it may have a protective role against fibre damage and necrosis.

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