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

ABSTRACT PROTEOLIPID protein (PLP; _M_r 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 _rumpshaker_6 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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS

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institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS MISSENSE MUTATION OF _MAL_ CAUSES A RARE LEUKODYSTROPHY SIMILAR TO

PELIZAEUS-MERZBACHER DISEASE Article Open access 25 February 2022 SUPPRESSION OF PROTEOLIPID PROTEIN RESCUES PELIZAEUS–MERZBACHER DISEASE Article 01 July 2020 HYPOMYELINATING

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Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Zentrum für Molekulare Biologie (ZMBH), Universität Heidelberg, D-6900, Heidelberg, Germany Armin Schneider, Paul

Montague & Klaus-Armin Nave * Applied Neurobiology Group, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK Paul Montague, Ian Griffiths, Monica Fanarraga & Peter Kennedy *

Department of Biological and Molecular Sciences, University of Stirling, Stirling, FK9 4LA, UK Peter Brophy Authors * Armin Schneider View author publications You can also search for this

author inPubMed Google Scholar * Paul Montague View author publications You can also search for this author inPubMed Google Scholar * Ian Griffiths View author publications You can also

search for this author inPubMed Google Scholar * Monica Fanarraga View author publications You can also search for this author inPubMed Google Scholar * Peter Kennedy View author

publications You can also search for this author inPubMed Google Scholar * Peter Brophy View author publications You can also search for this author inPubMed Google Scholar * Klaus-Armin

Nave View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 14 April 1992 * Accepted: 09 July 1992 * Issue Date: 27 August 1992 * DOI: https://doi.org/10.1038/358758a0 SHARE THIS ARTICLE

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