title: Proteolipid protein cannot replace P0 protein as the major structural protein of peripheral nervous system myelin.
abstract: The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when proteolipid protein (PLP) replaced P0 protein as the most abundant protein of CNS myelin. However, PLP did not replace P0 in peripheral nervous system (PNS) myelin. To investigate the possible consequences of a PLP to P0 shift in PNS myelin, we engineered mice to express PLP instead of P0 in PNS myelin (PLP-PNS mice). PLP-PNS mice had severe neurological disabilities and died between 3 and 6 months of age. Schwann cells in sciatic nerves from PLP-PNS mice sorted axons into one-to-one relationships but failed to form myelin internodes. Mice with equal amounts of P0 and PLP had normal PNS myelination and lifespans similar to wild-type (WT) mice. When PLP was overexpressed with one copy of the P0 gene, sciatic nerves were hypomyelinated; mice displayed motor deficits, but had normal lifespans. These data support the hypothesis that while PLP can co-exist with P0 in PNS myelin, PLP cannot replace P0 as the major structural protein of PNS myelin.
authors: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Xinghua
authors: X
authors: Yin
authors: Sumiko
authors: S
authors: Kiryu-Seo
authors: Grahame J
authors: GJ
authors: Kidd
authors: M Laura
authors: ML
authors: Feltri
authors: Lawrence
authors: L
authors: Wrabetz
authors: Bruce D
authors: BD
authors: Trapp
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D051379:Mice; D018993:Myelin P0 Protein / Q000235:genetics / Q000378:metabolism*; D018991:Myelin Proteolipid Protein / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D017933:Peripheral Nervous System / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism
chemical_list: D018993:Myelin P0 Protein; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein
keywords: Schwann cell; axon; hypomyelination; myelin compaction; myelin evolution