Tay-Sachs and Sandhoff diseases are autosomal recessive disorders of GM2 ganglioside catabolism resulting from deficient activity of lysosomal beta-hexosaminidase A (Hex A) or Hex A and Hex B, respectively. This leads to a massive and fatal accumulation of GM2 ganglioside in the neurons of affected patients. Mouse models of Tay-Sachs and Sandhoff diseases, created via targeted disruption of the Hexa and Hexb genes, revealed that while Hexb -/- mice suffer a profound, fatal neurodegenerative disease as expected, Hexa -/- mice escape disease to about one year. This protection is conferred by an ability to degrade GM2 ganglioside by means of a lysosomal sialidase mediated metabolic bypass. To determine if such a bypass could be made to function in humans, a series of experiments were performed to examine and compare the activity of mouse and human lysosomal sialidases in their ability to promote GM2 catabolism. The results suggest that human lysosomal sialidase, though sluggish, can indeed degrade GM2 when induced sufficiently.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.29893 |
| Date | January 1999 |
| Creators | Gafuik, Chris. |
| Contributors | Gravel, Roy (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 Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001686559, proquestno: MQ55059, Theses scanned by UMI/ProQuest. |
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