Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia.

J M Edgar, M. McLaughlin, Donald Yool, S C Zhang, J H Fowler, Paul Montague, J A Barrie, M C McCulloch, Ian Duncan, J Garbern, Klaus-Armin Nave, I R Griffiths

Research output: Contribution to journalArticlepeer-review


Oligodendrocytes are critical for the development of the plasma membrane and cytoskeleton of the axon. In this paper, we show that fast axonal transport is also dependent on the oligodendrocyte. Using a mouse model of hereditary spastic paraplegia type 2 due to a null mutation of the myelin Plp gene, we find a progressive impairment in fast retrograde and anterograde transport. Increased levels of retrograde motor protein subunits are associated with accumulation of membranous organelles distal to nodal complexes. Using cell transplantation, we show categorically that the axonal phenotype is related to the presence of the overlying Plp null myelin. Our data demonstrate a novel role for oligodendrocytes in the local regulation of axonal function and have implications for the axonal loss associated with secondary progressive multiple sclerosis.
Original languageEnglish
Pages (from-to)121-31
JournalJournal of Cell Biology
Issue number1
Publication statusPublished - 5 Jul 2004


  • Alleles
  • Animals
  • Axons/metabolism
  • Biological Transport
  • Blotting, Western
  • Cell Membrane/metabolism
  • Cytoskeleton/metabolism
  • Disease Models, Animal
  • Heterozygote
  • Immunohistochemistry
  • Mice
  • Mice, Mutant Strains
  • Myelin Sheath/metabolism
  • Oligodendroglia/metabolism
  • Optic Nerve/metabolism
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spastic Paraplegia, Hereditary/genetics
  • Spastic Paraplegia, Hereditary/metabolism
  • Spastic Paraplegia, Hereditary/pathology
  • Spinal Cord/pathology
  • Time Factors


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