Assembly of CNS myelin in the absence of proteolipid protein

Neuron. 1997 Jan;18(1):59-70. doi: 10.1016/s0896-6273(01)80046-5.


Two proteolipid proteins, PLP and DM20, are the major membrane components of central nervous system (CNS) myelin. Mutations of the X-linked PLP/DM20 gene cause dysmyelination in mouse and man and result in significant mortality. Here we show that mutant mice that lack expression of a targeted PLP gene fail to exhibit the known dysmyelinated phenotype. Unable to encode PLP/DM20 or PLP-related polypeptides, oligodendrocytes are still competent to myelinate CNS axons of all calibers and to assemble compacted myelin sheaths. Ultrastructurally, however, the electron-dense 'intraperiod' lines in myelin remain condensed, correlating with its reduced physical stability. This suggests that after myelin compaction, PLP forms a stabilizing membrane junction, similar to a "zipper." Dysmyelination and oligodendrocyte death emerge as an epiphenomenon of other PLP mutations and have been uncoupled in the PLP null allele from the risk of premature myelin breakdown.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System / pathology*
  • Central Nervous System / physiopathology*
  • DNA Primers
  • Demyelinating Diseases / genetics*
  • Demyelinating Diseases / pathology
  • Disease Models, Animal
  • Exons
  • Humans
  • Mice
  • Mice, Transgenic
  • Motor Activity*
  • Myelin Proteins / biosynthesis
  • Myelin Proteins / isolation & purification
  • Myelin Proteolipid Protein / biosynthesis
  • Myelin Proteolipid Protein / genetics*
  • Myelin Sheath / pathology
  • Myelin Sheath / physiology*
  • Myelin Sheath / ultrastructure
  • Nerve Tissue Proteins*
  • Polymerase Chain Reaction
  • Stem Cells
  • X Chromosome


  • DNA Primers
  • Myelin Proteins
  • Myelin Proteolipid Protein
  • Nerve Tissue Proteins
  • Plp1 protein, mouse