Caenorhabditis elegans clk-1(qm30) and isp-1(qm150) mutants exhibit highly pleiotropic phenotypes that include slow development and long lifespan. clk-1(qm30) and isp-1(qm150) correspond to loss of function mutations in genes necessary for ubiquinone biosynthesis and complex III electron transport, respectively. Previous research has lead to the hypothesis that altered levels of cellular reactive oxygen species (ROS) may underlie clk-1(qm30) and isp-1(qm150) mutant phenotypes. To test this hypothesis RNA interference (RNAi) by feeding was used to indirectly alter cellular ROS levels by knocking down genes that encode ROS detoxification enzymes. Specifically, genes that detoxify ROS using glutathione or thioredoxin, both of which are important cellular thiol-redox molecules, were knocked down to examine the role of ROS in determining clk-1(qm30) and isp-1(qm150) lifespan, post-embryonic development, and germline development. In summary, knocking down ROS detoxification genes does not severely appear to affect the phenotypes that were studied. ROS detoxification gene knockdowns consistently induced mild decreases in wild type, clk-1(qm30), and isp-1(qm150) lifespan. However, knocking down NAD+-dependent isocitrate dehydrogenases, which are not closely involved in ROS detoxification, similarly affected lifespan, indicating that decreases are not specific to ROS detoxification. Of note, knocking down gcs-1, which is required for glutathione biosynthesis, induced lethal intestinal abnormalities in wild type, c1k-1(qm30), and isp-1(qm150) worms. Overall, findings do not support that low ROS underlies the clk-1(qm30) and isp-1(qm150) mutant phenotypes.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.101597 |
| Date | January 2006 |
| Creators | Lee, Sansan. |
| 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 | © Sansan Lee, 2006 |
| Relation | alephsysno: 002592781, proquestno: AAIMR32738, Theses scanned by UMI/ProQuest. |
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