title: Myelin proteolipid proteins promote the interaction of oligodendrocytes and axons.
abstract: Although proteolipid protein (PLP) and its DM20 isoform are the major membrane proteins of CNS myelin, their absence causes surprisingly few developmental defects. In comparison, missense mutations of the X-linked Plp gene cause severe dysmyelination. Previous studies have established roles for PLP/DM20 in the formation of the intraperiod line and in maintaining axonal integrity. We now show that a normal number of oligodendrocytes are present in mice lacking PLP/DM20. However, in heterozygous females, which are natural chimeras for X-linked genes, oligodendrocytes lacking PLP/DM20 are in direct competition with wild-type oligodendrocytes that have a distinct advantage. PLP+ oligodendrocytes and PLP+ myelin sheaths make up the greater majority, and this feature is generalised in the CNS throughout life. Moreover, in the absence of PLP/DM20, a proportion of small-diameter axons fails to myelinate, remaining ensheathed but lacking a compact sheath, or show delayed myelination. These findings suggest that PLP/DM20 is also involved in the early stages of axon-oligodendrocyte interaction and wrapping of the axon.
authors.affiliation: Applied Neurobiology Group, Department of Veterinary Clinical Studies, University of Glasgow, Bearsden, Glasgow C61 1QH, Scotland.
authors.forename: D A
authors.initials: DA
authors.lastname: Yool
authors.forename: M
authors.initials: M
authors.lastname: Klugmann
authors.forename: M
authors.initials: M
authors.lastname: McLaughlin
authors.forename: D A
authors.initials: DA
authors.lastname: Vouyiouklis
authors.forename: L
authors.initials: L
authors.lastname: Dimou
authors.forename: J A
authors.initials: JA
authors.lastname: Barrie
authors.forename: M C
authors.initials: MC
authors.lastname: McCulloch
authors.forename: K A
authors.initials: KA
authors.lastname: Nave
authors.forename: I R
authors.initials: IR
authors.lastname: Griffiths
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018991:Myelin Proteolipid Protein / Q000172:deficiency* / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure
chemical_list: D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; C047516:Plp1 protein, mouse