P0 glycoprotein overexpression causes congenital hypomyelination of peripheral nerves

Lawrence Wrabetz, Maria Laura Feltri, Angelo Quattrini, Daniele Imperiale, Stefano Previtali, Maurizio D'Antonio, Rudolf Martini, Xinghua Yin, Bruce D. Trapp, Lei Zhou, Shing Yan Chiu, Albee Messing

Research output: Contribution to journalArticlepeer-review


We show that normal peripheral nerve myelination depends on strict dosage of the most abundantly expressed myelin gene, myelin protein zero (Mpz). Transgenic mice containing extra copies of Mpz manifested a dose-dependent, dysmyelinating neuropathy, ranging from transient perinatal hypomyelination to arrested myelination and impaired sorting of axons by Schwann cells. Myelination was restored by breeding the transgene into the Mpz-null background, demonstrating that dysmyelination does not result from a structural alteration or Schwann cell-extrinsic effect of the transgenic P0 glycoprotein. Mpz mRNA overexpression ranged from 30-700%, whereas an increased level of P0 protein was detected only in nerves of low copy-number animals. Breeding experiments placed the threshold for dysmyelination between 30 and 80% Mpz overexpression. These data reveal new points in nerve development at which Schwann cells are susceptible to increased gene dosage, and suggest a novel basis for hereditary neuropathy.

Original languageEnglish
Pages (from-to)1021-1033
Number of pages13
JournalJournal of Cell Biology
Issue number5
Publication statusPublished - Mar 6 2000


  • Axon sorting
  • Myelin
  • Neuropathy
  • Schwann cell
  • Transgene

ASJC Scopus subject areas

  • Cell Biology


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