| First Author | Wrabetz L | Year | 2000 |
| Journal | J Cell Biol | Volume | 148 |
| Issue | 5 | Pages | 1021-34 |
| PubMed ID | 10704451 | Mgi Jnum | J:78758 |
| Mgi Id | MGI:2386073 | Doi | 10.1083/jcb.148.5.1021 |
| Citation | Wrabetz L, et al. (2000) P(0) glycoprotein overexpression causes congenital hypomyelination of peripheral nerves. J Cell Biol 148(5):1021-34 |
| abstractText | 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 P(0) glycoprotein. Mpz mRNA overexpression ranged from 30-700%, whereas an increased level of P(0) 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. |
