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Absence of P0 leads to the dysregulation of myelin gene expression and myelin morphogenesis
Author(s) -
Xu Wenbo,
Manichella Daniela,
Jiang Huiyuan,
Vallat JeanMichel,
Lilien Jack,
Baron Pierluigi,
Scarlato Guglielmo,
Kamholz John,
Shy Michael E.
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/1097-4547(20000615)60:6<714::aid-jnr3>3.0.co;2-1
Subject(s) - myelin , proteolipid protein 1 , microbiology and biotechnology , biology , peripheral myelin protein 22 , mutant , cell adhesion molecule , gene expression , gene , myelin basic protein , central nervous system , genetics , neuroscience
P0, the major peripheral nervous system (PNS) myelin protein, is a member of the immunoglobulin supergene family of membrane proteins and can mediate homotypic adhesion. P0 is an essential structural component of PNS myelin; mice in which P0 expression has been eliminated by homologous recombination (P0−/−) develop a severe dysmyelinating neuropathy with predominantly uncompacted myelin. Although P0 is thought to play a role in myelin compaction by promoting adhesion between adjacent extracellular myelin wraps, as an adhesion molecule it could also have a regulatory function. Consistent with this hypothesis, Schwann cells in adult P0−/− mice display a novel molecular phenotype: PMP22 expression is down‐regulated, MAG and PLP expression are up‐regulated, and MBP expression is unchanged. As in quaking viable mutant mice ( qk v ), which have uncompacted myelin morphologically similar to that found in P0−/− mice, neither the qKI‐6 or qKI‐7 proteins are expressed in P0−/− peripheral nerve. In addition to these changes in gene expression in the P0 knockout, PLP/DM‐20 accumulates in the endoplasmic reticulum of P0−/− Schwann cells, whereas MAG accumulates in redundant loops of uncompacted myelin, not at nodes of Ranvier or Schmidt‐Lantermann incisures. Taken together, these results demonstrate that P0 is involved, either directly or indirectly, in the regulation of both myelin gene expression and myelin morphogenesis. J. Neurosci. Res. 60:714–724, 2000. © 2000 Wiley‐Liss, Inc.