title: Assembly of CNS myelin in the absence of proteolipid protein.
abstract: 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.
authors.affiliation: Zentrum für Molekulare Biologie (ZMBH) University of Heidelburg, Federal Republic of Germany.
authors.forename: M
authors.initials: M
authors.lastname: Klugmann
authors.forename: M H
authors.initials: MH
authors.lastname: Schwab
authors.forename: A
authors.initials: A
authors.lastname: Pühlhofer
authors.forename: A
authors.initials: A
authors.lastname: Schneider
authors.forename: F
authors.initials: F
authors.lastname: Zimmermann
authors.forename: I R
authors.initials: IR
authors.lastname: Griffiths
authors.forename: K A
authors.initials: KA
authors.lastname: Nave
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000473:pathology* / Q000503:physiopathology*; D017931:DNA Primers; D003711:Demyelinating Diseases / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005091:Exons; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009185:Myelin Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D018991:Myelin Proteolipid Protein / Q000096:biosynthesis / Q000235:genetics*; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins; D016133:Polymerase Chain Reaction; D013234:Stem Cells; D014960:X Chromosome
chemical_list: D017931:DNA Primers; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; C047516:Plp1 protein, mouse