| Autor: |
Joshua Colby, Robert Nicholson, Kathleen M. Dickson, Wayel Orfali, Roland Naef, Ueli Suter, G.Jackson Snipes |
| Jazyk: |
angličtina |
| Rok vydání: |
2000 |
| Předmět: |
|
| Zdroj: |
Neurobiology of Disease, Vol 7, Iss 6, Pp 561-573 (2000) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1006/nbdi.2000.0323 |
| Popis: |
Missense mutations in the murine peripheral myelin protein-22 gene (Pmp22) underly the neuropathies in the trembler (Tr) and trembler-J (Tr-J) mice and in some humans with Charcot-Marie-Tooth disease. We have generated replication-defective adenoviruses containing epitope-tagged, wild-type-, Tr-, or Tr-J-PMP22 bicistronic with the Lac-Z reporter gene. These viruses were microinjected into the sciatic nerves of 10-day-old Sprague–Dawley rats and, later, analyzed by immunohistochemistry to determine the distribution of mutant protein in infected myelinating Schwann cells. We found that epitope-tagged, wild-type PMP22 is successfully transported to compact myelin, whereas the Tr and the Tr-J mutant proteins are retained in cytoplasmic compartment, colocalizing with the endoplasmic reticulum. These results provide in vivo evidence that the pathogenesis of the Tr and Tr-J mutations are most likely a function of abnormal retention within the endoplasmic reticulum of myelinating Schwann cells. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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