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Studies on the effects of altered PMP22 expression during myelination in vitro
Author(s) -
D'Urso Donatella,
Schmalenbach Corinne,
Zoidl Georg,
Prior Reinhard,
Müller Hans Werner
Publication year - 1997
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/(sici)1097-4547(19970401)48:1<31::aid-jnr3>3.0.co;2-f
Subject(s) - myelin , peripheral myelin protein 22 , biology , schwann cell , gene duplication , microbiology and biotechnology , myelin associated glycoprotein , pathology , gene , central nervous system , neuroscience , genetics , medicine
Severe inherited dysmyelinating diseases of the peripheral nervous system, the Charcot‐Marie‐Tooth type1A disease (CMT1A) and the hereditary neuropathy with liability to pressure palsies (HNPP) are associated with a large DNA duplication or deletion of a chromosomal region containing the peripheral myelin protein 22 (PMP22) gene. It has been suggested that a gene dosage effect involving PMP22 is responsible for the pathological phenotype. We investigated if altered PMP22 expression affects the onset of myelin formation and the ultrastructure of myelin. Rat Schwann cell cultures were stably infected with recombinant retrovirus vectors harboring the rat PMP22 cDNA in sense or antisense orientation. Schwann cells over‐ or underexpressing PMP22 were cocultured with purified DRG neurons under conditions that promote myelination. We examined PMP22 expression and localization in the myelin forming cultures by RT‐PCR, immunohistochemistry and confocal microscopy, and we analyzed myelin ultrastructure by electron microscopy. Our results demonstrate that abnormal levels of PMP22 expression do not impair the early stages of myelination and membrane compaction and do not interfere with the expression of other myelin genes. Our observations further indicate that PMP22 is involved more in controlling myelin thickness and stability than in the events determining the initial steps of myelin formation. J. Neurosci. Res. 48:31–42, 1997. © 1977 Wiley‐Liss, Inc.