Schwann cell expression of PLP1 but not DM20 is necessary to prevent neuropathy

Michael E. Shy, Grace Hobson, Manisha Jain, Odile Boespflug-Tanguy, James Garbern, Karen Sperle, Wen Li, Alex Gow, Diana Rodriguez, Enrico Bertini, Pedro Mancias, Karen Krajewski, Richard Lewis, John Kamholz

Research output: Contribution to journalArticle

Abstract

Proteolipid protein (PLP1) and its alternatively spliced isoform, DM20, are the major myelin proteins in the CNS, but are also expressed in the PNS. The proteins have an identical sequence except for 35 amino acids in PLP1 (the PLP1-specific domain) not present in DM20. Mutations of PLP1/DM20 cause Pelizaeus-Merzbacher Disease (PMD), a leukodystrophy, and in some instances, a peripheral neuropathy. To identify which mutations cause neuropathy, we have evaluated a cohort of patients with PMD and PLP1 mutations for the presence of neuropathy. As shown previously, all patients with PLP1 null mutations had peripheral neuropathy. We also identified 4 new PLP1 point mutations that cause both PMD and peripheral neuropathy, three of which truncate PLP1 expression within the PLP1-specific domain, but do not alter DM20. The fourth, a splicing mutation, alters both PLP1 and DM20, and is probably a null mutation. Six PLP1 point mutations predicted to produce proteins with an intact PLP1-specific domain do not cause peripheral neuropathy. Sixty-one individuals with PLP1 duplications also had normal peripheral nerve function. These data demonstrate that expression of PLP1 but not DMSO is necessary to prevent neuropathy, and suggest that the 35 amino acid PLPl-specific domain plays an important role in normal peripheral nerve function.

Original languageEnglish
Pages (from-to)354-365
Number of pages12
JournalAnnals of Neurology
Volume53
Issue number3
DOIs
Publication statusPublished - Mar 1 2003

ASJC Scopus subject areas

  • Neuroscience(all)

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    Shy, M. E., Hobson, G., Jain, M., Boespflug-Tanguy, O., Garbern, J., Sperle, K., Li, W., Gow, A., Rodriguez, D., Bertini, E., Mancias, P., Krajewski, K., Lewis, R., & Kamholz, J. (2003). Schwann cell expression of PLP1 but not DM20 is necessary to prevent neuropathy. Annals of Neurology, 53(3), 354-365. https://doi.org/10.1002/ana.10466