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Longitudinal locomotion assessment to study neurodegeneration in C. elegans models of tauopathies

Schweighauser, Gabriel. Longitudinal locomotion assessment to study neurodegeneration in C. elegans models of tauopathies. 2017, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_12844

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Abstract

Tauopathies are a group of neurodegenerative diseases defined by the aggregation of abnormally phosphorylated protein tau. The cause for neurodegeneration observed in tauopathies is not known. The discovery of mutations in the gene encoding for tau in familial cases of FTDP-17, a hereditary tauopathy, emphasized the importance of tau in these diseases. This led to the creation of animal models expressing human tau containing mutations found in FTDP-17, recapitulating some of the aspects of the disease, including neurodegeneration and tau aggregation. Reports on the consequences of human tau expression in the neurons of C. elegans are partially contradictory, especially with regard to their locomotor phenotype. In this work, we replicated C. elegans models of tauopathies and performed immunohistochemical and locomotion assessments. We created 23 genomically integrated strains pan-neuronally expressing either wild type or mutated human tau. In agreement with published reports, immunohistochemistry revealed no difference between wild type or mutated human tau with regard to phosphorylation status. To obtain lifelong, longitudinal recordings of several hundred worms, we developed a novel worm tracking system which we termed Robot-Assisted Plate Imaging Device (RAPID). Using RAPID, we recorded the stimulated locomotor performance of human tau-expressing worms, exceeding the number of all reported observations combined by two orders of magnitude. Our data indicate no pronounced locomotor phenotype in those transgenic worms, arguing against the reported neurotoxic effect of tau in C. elegans.
Advisors:Stahlberg, Henning and Tolnay, Markus and Glauser, Dominique
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Stahlberg)
UniBasel Contributors:Stahlberg, Henning and Tolnay, Markus
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:12844
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (151 Seiten)
Language:English
Identification Number:
Last Modified:11 Dec 2018 05:30
Deposited On:10 Dec 2018 16:07

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