Brain, Vol. 116, No. 2, 325-336, 1993
© 1993 Oxford University Press
research-article |
Mitochondrial DNA deletions in inclusion body myositis
1Pathology Gothenburg, Sweden 2Clinical Chemistry Gothenburg, Sweden 3Neurology, Gothenburg University Gothenburg, Sweden
Correspondence to:
Correspondence to: Dr Anders Oldfors, Department of Pathology, Sahlgren's Hospital, S-413 45 Göteborg, Sweden.
Skeletal muscle specimens from three patients with inclusion body myositis, aged 39, 60 and 71 years, respectively, were investigated. Enzyme histochemical staining of cytochrome c oxidase (COX), succinate dehydrogenase and myofibrillar ATPase, and in situ hybridization of transcripts of mitochondrial DNA (mtDNA) were performed on consecutive sections. In all three cases a proportion of muscle fibres (2–5%) showed low or absent COX activity in spite of medium or high succinate dehydrogenase activity (COX deficient muscle fibres). Two probes detecting transcripts of different segments of mtDNA were used for the in situ hybridization. One of the probes (ND4 probe) detected transcripts of a segment of the NADH dehydrogenase subunit 4 gene, which is known to be affected in most cases of mitochondrial myopathy with large deletions of mtDNA. There was reduced hybridization of the ND4 probe in many COX deficient muscle fibres compared with adjacent normal fibres. The other probe (ND2 probe) detected transcripts of a segment of the NADH dehydrogenase subunit 2 gene, which usually is not included in mtDNA deletions. There was accumulation of transcripts corresponding to the ND2 probe in COX deficient fibres in all three cases. These findings demonstrate that deleted mtDNA had accumulated in COX deficient muscle fibres in patients with inclusion body myositis. Southern blot analysis of mtDNA in muscle revealed a 16.6 kb fragment corresponding to normal mtDNA in all three cases. In one case two additional less abundant fragments of smaller size, corresponding to deleted mtDNA, were detected. Ultrastructural investigation showed abnormal mitochondria in all three cases. Control muscle specimens were obtained from nine patients, aged 63 – 71 years, with muscle pain but without morphological evidence of muscle disease. Occasional COX deficient fibres (< 1%) were found in three of the control cases. The other six control cases showed no COX deficient fibres.
Our results show that mtDNA deletions may be involved in the pathogenesis of inclusion body myositis and cause respiratory chain dysfunction in muscle fibre segments.
Received July 23, 1992. Revised October 15, 1992. Accepted October 26, 1992.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Chahin and A. G. Engel Correlation of muscle biopsy, clinical course, and outcome in PM and sporadic IBM Neurology, February 5, 2008; 70(6): 418 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Oldfors, A. R. Moslemi, L. Jonasson, M. Ohlsson, G. Kollberg, and C. Lindberg Mitochondrial abnormalities in inclusion-body myositis Neurology, January 24, 2006; 66(1_suppl_1): S49 - S55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sorensen, M. Ekstrand, J. P. Silva, E. Lindqvist, B. Xu, P. Rustin, L. Olson, and N.-G. Larsson Late-Onset Corticohippocampal Neurodepletion Attributable to Catastrophic Failure of Oxidative Phosphorylation in MILON Mice J. Neurosci., October 15, 2001; 21(20): 8082 - 8090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wyss and R. Kaddurah-Daouk Creatine and Creatinine Metabolism Physiol Rev, July 1, 2000; 80(3): 1107 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Uusimaa, A. M. Remes, H. Rantala, L. Vainionpää, R. Herva, K. Vuopala, M. Nuutinen, K. Majamaa, and I. E. Hassinen Childhood Encephalopathies and Myopathies: A Prospective Study in a Defined Population to Assess the Frequency of Mitochondrial Disorders Pediatrics, March 1, 2000; 105(3): 598 - 603. [Abstract] [Full Text]
|
|