Mutant quaking viable mice (qkV) develop a tremor phenotype in their hind limbs 10 days after birth, likely resulting from severe myelination defects. Genetically, quaking viable mice contain a deletion in the promoter/enhancer region of the quaking gene. The quaking gene is alternatively spliced, producing QUAKING isoforms that differ in their C-terminal amino acid sequence. The QKI-5 isoform is nuclear, whereas the QKI-6 and QKI-7 isoforms are predominantly cytoplasmic. The QKI isoforms contain a single KH RNA-binding domain, which suggests a role in RNA metabolism. Although the dysmyelinating phenotype of the mutant mice suggests a role in myelination, the function of the protein remains largely unknown. The objective of this thesis is to characterize the role of the RNA binding proteins QKI in the differentiation of glial cells and their involvement in the process of myelination. Moreover, this study describes the quaking viable defects and how the isoforms contribute to the observed phenotype. [...] / Les protéines liant l’ARN jouent un rôle central afin de contrôler l’expression génique, l’épissage alternatif et la localisation des ARN messagers. Pour qu’une cellule se différencie, les gènes doivent être régulés au niveau de leur expression et de la localisation de leurs ARNm. Un des phénomènes physiologique de différentiation au niveau du système nerveux est la myélinisation des axones. En vulgarisant, la gaine de myéline serait l’isolant entourant le fil électrique étant l’axone. [...]
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.97774 |
| Date | January 2004 |
| Creators | Larocque, Daniel |
| Contributors | Richard, Stéphane (Supervisor) |
| 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 | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 003494105, Theses scanned by McGill Library. |
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