The cytoplasmic domain of the large myelin-associated glycoprotein isoform is needed for proper CNS but not peripheral nervous system myelination

Nobuya Fujita, April Kemper, Jeffrey Dupree, Hiroyuki Nakayasu, Udo Bartsch, Melitta Schachner, Nobuyo Maeda, Kinuko Suzuki, Kunihiko Suzuki, Brian Popko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

The myelin-associated glycoprotein (MAG) is a member of the immunoglobulin gene superfamily and is thought to play a critical role in the interaction of myelinating glial cells with the axon. Myelin from mutant mice incapable of expressing MAG displays various subtle abnormalities in the CNS and degenerates with age in the peripheral nervous system (PNS). Two distinct isoforms, large MAG (L-MAG) and small MAG (S-MAG), are produced through the alternative splicing of the primary MAG transcript. The cytoplasmic domain of L-MAG contains a unique phosphorylation site and has been shown to associate with the fyn tyrosine kinase. Moreover, L-MAG is expressed abundantly early in the myelination process, possibly indicating an important role in the initial stages of myelination. We have adapted the gene-targeting approach in embryonic stem cells to generate mutant mice that express a truncated form of the L-MAG isoform, eliminating the unique portion of its cytoplasmic domain, but that continue to express S-MAG. Similar to the total MAG knockouts, these animals do not express an overt clinical phenotype. CNS myelin of the L-MAG mutant mice displays most of the pathological abnormalities reported for the total MAG knockouts. In contrast to the null MAG mutants, however, PNS axons and myelin of older L-MAG is sufficient to maintain PNS integrity. These observations demonstrate a differential role of the L-MAG isoform in CNS and PNS myelin.

Original languageEnglish (US)
Pages (from-to)1970-1978
Number of pages9
JournalJournal of Neuroscience
Volume18
Issue number6
DOIs
StatePublished - Mar 15 1998

Keywords

  • Alternative RNA splicing
  • Gene knockout
  • Mouse models
  • Myelin-associated glycoprotein
  • Oligodendrocytes
  • Schwann cells

ASJC Scopus subject areas

  • Neuroscience(all)

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