Expressing antisense P0 RNA in Schwann cells perturbs myelination.
Primary Schwann cells were infected in vitro with a recombinant retrovirus expressing a dominant selectable marker, neomycin phosphotransferase (conferring resistance to the drug G418), and antisense P0 RNA under the control of the human beta-actin promoter. A proportion of the G418-resistant cells failed to form myelin when cocultured with dorsal root ganglion neurons under conditions that promote Schwann cell differentiation. These cells expressed high levels of P0 antisense RNA. Among the impaired cells, the majority had segregated and ensheathed individual axon but had not differentiated further. They did not express P0 but did express myelin- associated glycoprotein and galactocerebroside. A minority of partially inhibited Schwann cells were also observed that elaborated thin myelin sheaths containing variable numbers of compacted and noncompacted lamellae. These data indicate that restricting the level of P0 expression inhibits spiralling of the Schwann cell membrane and subsequent compaction.
Owens
G C
GC
Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110.
Boyd
C J
CJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004352:Drug Resistance, Microbial; D005699:Galactosylceramides / Q000502:physiology; D019868:Kanamycin Kinase; D008854:Microscopy, Electron; D018993:Myelin P0 Protein; D009185:Myelin Proteins / Q000235:genetics / Q000502:physiology*; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D018992:Myelin-Associated Glycoprotein; D010525:Peripheral Nerves / Q000502:physiology*; D010770:Phosphotransferases / Q000502:physiology; D016372:RNA, Antisense / Q000502:physiology*; D051381:Rats; D012192:Retroviridae Infections; D012583:Schwann Cells / Q000382:microbiology / Q000502:physiology* / Q000648:ultrastructure
D005699:Galactosylceramides; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D016372:RNA, Antisense; D010770:Phosphotransferases; D019868:Kanamycin Kinase