Deciphering peripheral nerve myelination by using Schwann cell expression profiling.
Although mutations in multiple genes are associated with inherited demyelinating neuropathies, the molecular components and pathways crucial for myelination remain largely unknown. To approach this question, we performed genome-wide expression analysis in several paradigms where the status of peripheral nerve myelination is dynamically changing. Anchor gene correlation analysis, a form of microarray analysis that integrates functional information, using correlation-based clustering, with a statistically rigorous test, the Westfall and Young step-down algorithm, was applied to this data set. Biological pathways active in myelination, genes encoding proteins involved in myelin synthesis, and genes whose mutation results in myelination defects were identified. Many known genes and previously uncharacterized ESTs not heretofore associated with myelination were also identified. One of these ESTs, MASR (myelin-associated SUR4 protein), encodes a member of the SUR4 family of fatty acid desaturases, enzymes involved in elongation of very long chain fatty acids. Its specific localization in myelinating Schwann cells indicates a crucial role for MASR in normal myelin lipid synthesis.
Nagarajan
Rakesh
R
Department of Pathology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8118, St. Louis, MO 63110, USA.
Le
Nam
N
Mahoney
Heather
H
Araki
Toshiyuki
T
Milbrandt
Jeffrey
J
D000818:Animals; D020224:Expressed Sequence Tags; D044943:Fatty Acid Desaturases / Q000378:metabolism; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*
D044943:Fatty Acid Desaturases