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The Study of Hereditary Spastic Paraplegia Genes Using Drosophila Homologues: Behavioural Insights
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- Author / Creator
- Strautman, Joel C
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Hereditary Spastic Paraplegia (HSP) denotes a heterogeneous group of heritable neurodegenerative disorders predominantly characterized by progressive weakness and spasticity of the legs. Mutations in the gene SPAST are by far the most common, while mutations in the gene ATL1 are the second most prevalent. Recently, a novel gene, DCNT1, has been implicated in HSP neuropathology. We used the Drosophila homologues of these three genes⎯D-spastin, D-atl, and Glued, respectively⎯to determine whether or not corresponding mutations are associated with locomotion deficits. We employed locomotion assays⎯i.e., climbing, walking, and larva tracking⎯and genetic tools available in Drosophila⎯i.e., genetic mutations and altered gene expression via the GAL4-UAS system⎯to manipulate the physiological function of these HSP genes at multiple developmental time points. This approach was employed to identify potential locomotion deficits resulting from mutations in single genes or alterations in their expression levels (Experimental Aim 1), or the interactions between different genes (Experimental Aim 2). We show evidence for a functional role of all three genes of interest in Drosophila locomotion, as well as for the pairwise interactions between them. However, the genetic interaction⎯i.e., the synergistic effect of a combination of two or more genetic manipulations⎯between D-spastin and D-atl is relatively inconclusive. The clustering of HSP genes via interaction data will not only aid in elucidating the convergent mechanisms underlying the disorder, but will also facilitate the development of potential treatments for HSP patients.
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- Graduation date
- Fall 2014
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- Type of Item
- Thesis
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- Degree
- Master of Science
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- License
- This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.