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Uncoupling of hypomyelination and glial cell death by a mutation in the proteolipid protein gene

Nature volume 358, pages 758–761 (1992)Cite this article

Abstract

PROTEOLIPID protein (PLP; Mr 30,000) is a highly conserved major polytopic membrane protein in myelin but its cellular function remains obscure. Neurological mutant mice can often provide model systems for human genetic disorders. Mutations of the X-chromosome-linked PLP gene are lethal, identified first in the jimpy mouse1,2 and subsequently in patients with PelizaeusMerzbacher disease3,4. The unexplained phenotype of these mutations includes degeneration and premature cell death of oligodendrocytes with associated hypomyelination5. Here we show that a new mouse mutant rumpshaker6 is defined by the amino-acid substitution Ile-to-Thr at residue 186 in a membrane-embedded domain of PLP. Surprisingly, rumpshaker mice, although myelindeficient, have normal longevity and a full complement of morphologically normal oligodendrocytes7. Hypomyelination can thus be genetically separated from the PLP-dependent oligodendrocyte degeneration. We suggest that PLP has a vital function in glial cell development, distinct from its later role in myelin assembly, and that this dichotomy of action may explain the clinical spectrum8 of Pelizaeus–Merzbacher disease.

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Authors and Affiliations

  1. Zentrum für Molekulare Biologie (ZMBH), Universität Heidelberg, D-6900, Heidelberg, Germany

    Armin Schneider, Paul Montague & Klaus-Armin Nave

  2. Applied Neurobiology Group, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK

    Paul Montague, Ian Griffiths, Monica Fanarraga & Peter Kennedy

  3. Department of Biological and Molecular Sciences, University of Stirling, Stirling, FK9 4LA, UK

    Peter Brophy

Authors
  1. Armin Schneider
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  2. Paul Montague
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  6. Peter Brophy
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  7. Klaus-Armin Nave
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Schneider, A., Montague, P., Griffiths, I. et al. Uncoupling of hypomyelination and glial cell death by a mutation in the proteolipid protein gene. Nature 358, 758–761 (1992). https://doi.org/10.1038/358758a0

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