Many hereditary peripheral neuropathies are characterized by abnormal myelination in peripheral nerves. Two structural myelin proteins, PMP22, a polytopic myelin protein, and P0, an Ig-like transmembrane protein, play a major role in myelin formation. A large number of mutations have been identified in P0 and PMP22 genes. Neuropathies associated with PMP22 and P0 mutations have varying severities suggesting their effects are pleiotropic. It is of great importance to explore molecular pathogenesis of mutated P0 and PMP22 proteins in order to understand the basic process of myelination and its pathology. We hypothesize that these mutations have a variety of effects on the cell biological processes, including activation of ER quality control mechanisms, abnormal intracellular trafficking, or disruption of normal function. In order to dissect these possible effects, we studied the intracellular distribution and trafficking of mutated forms of PMP22 and P0 proteins in mammalian cells. Our studies indicate that the various P0 and PMP22 mutants may exert their pathogenic effects in different compartments and by different mechanisms in the mammalian cell.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.79122 |
| Date | January 2002 |
| Creators | Shames, Igor |
| Contributors | Richardson, J. B. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Pathology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001974966, proquestno: AAIMQ88291, Theses scanned by UMI/ProQuest. |
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