Survival of, and competition between, oligodendrocytes expressing different alleles of the Plp gene

J. M. Edgar, T. J. Anderson, Peter J Dickinson, J. A. Barrie, M. C. McCulloch, K. A. Nave, I. R. Griffiths

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Mutations in the X-linked Plp gene lead to dysmyelinating phenotypes and oligodendrocyte cell death. Here, we exploit the X inactivation phenomenon to show that a hierarchy exists in the influence of different mutant Plp alleles on oligodendrocyte survival. We used compound heterozygote mice to study the long-term fate of oligodendrocytes expressing either the jimpy or rumpshaker allele against a background of cells expressing a Plp-null allele. Although mutant and null oligodendrocytes were generated in equal numbers, the proportion expressing the mutant allele subsequently declined, but whereas those expressing the rumpshaker allele formed a reduced but stable population, the number of jimpy cells fell progressively. The age of decline in the jimpy cells in different regions of the CNS correlated with the temporal sequence of myelination. In compound heterozygotes expressing rumpshaker and jimpy alleles, oligodendrocytes expressing the former predominated and were more abundant than when the rumpshaker and null alleles were in competition. Thus, oligodendrocyte survival is not determined solely by cell intrinsic factors, such as the conformation of the misfolded PLP, but is influenced by neighboring cells, possibly competing for cell survival factors.

Original languageEnglish (US)
Pages (from-to)719-729
Number of pages11
JournalJournal of Cell Biology
Volume158
Issue number4
DOIs
StatePublished - Aug 19 2002
Externally publishedYes

Keywords

  • Heterozygote
  • Mutation
  • Myelin protein
  • Oligodendrocyte
  • Proteolipid protein

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Edgar, J. M., Anderson, T. J., Dickinson, P. J., Barrie, J. A., McCulloch, M. C., Nave, K. A., & Griffiths, I. R. (2002). Survival of, and competition between, oligodendrocytes expressing different alleles of the Plp gene. Journal of Cell Biology, 158(4), 719-729. https://doi.org/10.1083/jcb.200202124