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Identification and molecular genetic characterization of a coq-4 knockout mutation in Caenorhabditis elegans

In Caenorhabditis elegans, mutations in the clk-1 gene result in delayed embryonic and post-embryonic development, a slowing down of rhythmic behaviors and an extended life span. CLK-1 encodes the demethoxyubiquinone (DMQ or DMQn) hydroxylase in the ubiquinone (CoQ or Qn) biosynthesis pathway. Thus, clk-1 mutants produce DMQ instead of CoQ. In order to understand the relationship between the CoQ biosynthesis defect and the pleiotropic phenotype of clk-1 mutants, I isolated a deletion mutant, coq-4(qm143), in C. elegans. In Saccharomyces cerevisiae, mutants in COQ4, the coq-4 homologue, do not produce ubiquinone, like those in COQ7, the clk-1 homologue. coq-4(qm143) is a non-strict maternal-effect lethal mutation. Most of the progeny from a homozygous coq-4(qm143) hermaphrodite die during embryogenesis. However, homozygous coq-4(qm143) hermaphrodites from a heterozygous mother can develop and behave normally until adulthood. As adults, they become uncoordinated and paralytic, and are defective in egg-laying. Unlike hermaphrodites, homozygous coq-4(qm143) males are fully maternally rescued. The qm143 is a 1469 base pair deletion, which completely removes the coq-4 gene and does not affect the coding sequence of any other gene. By performing germline transformation, I also showed that the non-viable phenotype of coq-4 (qm143) is indeed due to the removal of the coq-4 gene itself. The preliminary study of COQ-4 expression pattern by using a COQ-4::GFP fusion protein indicates that COQ-4 is expressed in mitochondria of the worm.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33769
Date January 2001
CreatorsHan, Dong, 1970-
ContributorsHekimi, S. (advisor)
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Department of Biology.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001873472, proquestno: MQ78886, Theses scanned by UMI/ProQuest.

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