The most common cause of human hereditary neuropathies is a duplication in the peripheral myelin protein-22 (PMP22) gene. PMP22 is an integral membrane glycoprotein expressed primarily in the compact myelin of the mammalian peripheral nervous system. The naturally-occurring Trembler, and Trembler-J mouse models of hereditary neuropathies carry non-conservative point mutations in the PMP22 gene and have been essential in developing the understanding of the cell biology of PMP22 mutants. However, the greatest limitation to the study of PMP22 mutant trafficking has been the lack of a good model of myelination. To address this, we have developed replication-defective recombinant adenoviruses to study the intracellular trafficking of epitope-tagged wild-type, Trembler, and Trembler-J PMP22 in vivo. We have determined that in myelinating Schwann cells in vivo, newly synthesized epitope-tagged wild-type PMP22 is incorporated into myelin whereas the PMP22 mutants, Trembler and Trembler-J, are intracellularly retained in the ER.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.30358 |
| Date | January 2000 |
| Creators | Colby, Joshua Joseph. |
| Contributors | Snipes, George Jackson (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: 001754414, proquestno: MQ64334, Theses scanned by UMI/ProQuest. |
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