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Alterations in myelination in the central nervous system of dystonia musculorum mice

Authors

  • Ron Saulnier,

    1. Ottawa Health Research Institute and The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada
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  • Yves De Repentigny,

    1. Ottawa Health Research Institute and The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada
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  • Voon Wee Yong,

    1. Neuroscience and Cancer Biology Research Groups, Departments of Oncology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
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  • Rashmi Kothary

    Corresponding author
    1. Ottawa Health Research Institute and The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada
    2. Department of Cellular and Molecular Medicine and Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    • Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada
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Abstract

Dystonia musculorum (dt) is an autosomal recessive sensory neuropathy in mice resulting from a mutation in the gene encoding the cytoskeletal linker protein Bpag1. In addition to neurodegeneration, dt mice display myelination abnormalities in the peripheral nervous system. In this report we investigated whether myelination abnormalities are also present in the central nervous system of dtTg4 mice. Transcripts for both neural isoforms of Bpag1 (a1 and a2) were detected in optic nerves and spinal cords of wild-type mice. Light microscopy of resin-embedded thin sections revealed a reduction in myelinated axons in both optic nerves and spinal cords in dtTg4 mice. As well, hypermyelinated axons were detected in these tissues. Ultrastructural analysis of optic nerves and spinal cords from dtTg4 mice revealed an increase in the number of amyelinated axons, the presence of hypo- and hypermyelinated axons, and redundant myelin that course away from axons. Changes in the level of myelin proteins accompanied the morphological alterations. Myelin-associated glycoprotein levels were reduced in optic nerves of dtTg4 mice, and myelin basic protein levels were altered in optic nerves, sciatic nerves, and spinal cords of affected mice. Short-term cultures of oligodendrocytes derived from dtTg4 mice did not show morphological alterations. © 2002 Wiley-Liss, Inc.

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