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Disruption of LDL receptor-like gene function in Caenorhabditis elegans

dsc-4(qm182), a mutation that suppresses the lengthened defecation cycle of clk-1 also suppresses the delay in germline development. dsc-4 encodes a putative orthologue of microsomal triglyceride transfer protein (MTP), a protein essential for the assembly and secretion of apo-B-containing low density lipoproteins (LDL). The effect of dsc-4 on clk-1(qm30), coupled to studies of apoB homologues in worms led to a model suggesting the possibility of using C. elegans in the study of LDL-like lipoprotein particles. The impact of the level of lipoproteins is particularly evident in the germline developmental rate of the worms. / We report here a further elucidation of clk-1 mutants in the study of the biology of LDL-like particles. In particular, we investigated the effect of targeting LDL receptor-like genes by RNA interference (RNAi) on the egg laying rate of clk-1(qm30). We find positive modulating effects by disruption of these putative LDL receptors. In confirmation of our model of lipoprotein metabolism in clk-1 mutants, we find that disruption of these putative LDL receptors produces strikingly different effects in wild-type, clk-1(qm30) or clk-1(qm30); dsc-4(qm182) animals. / In addition, we report unexpected effects of various clk-1 alleles on the phenotypes of animals in which lrp-1 and rme-2 are disrupted. Specifically, we observe an allele specific amelioration of the phenotypes associated with disruption of these genes (abnormal molting and sterility, respectively). We discuss the possible significance of these findings. (Abstract shortened by UMI.)

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.81419
Date January 2004
CreatorsOviedo Landaverde, Irene
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: 002182943, proquestno: AAIMR06434, Theses scanned by UMI/ProQuest.

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