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Assaying β-amyloid Toxicity using a Transgenic C. elegans Model

Accumulation of the β-amyloid peptide (Aβ) is generally believed to be central to the induction of Alzheimer's disease, but the relevant mechanism(s) of toxicity are still unclear. Aβ is also deposited intramuscularly in Inclusion Body Myositis, a severe human myopathy. The intensely studied ne...

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Autores principales: Dostal, Vishantie, Link, Christopher D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MyJove Corporation 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185644/
https://www.ncbi.nlm.nih.gov/pubmed/20972410
http://dx.doi.org/10.3791/2252
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author Dostal, Vishantie
Link, Christopher D.
author_facet Dostal, Vishantie
Link, Christopher D.
author_sort Dostal, Vishantie
collection PubMed
description Accumulation of the β-amyloid peptide (Aβ) is generally believed to be central to the induction of Alzheimer's disease, but the relevant mechanism(s) of toxicity are still unclear. Aβ is also deposited intramuscularly in Inclusion Body Myositis, a severe human myopathy. The intensely studied nematode worm Caenorhabditis elegans can be transgenically engineered to express human Aβ. Depending on the tissue or timing of Aβ expression, transgenic worms can have readily measurable phenotypes that serve as a read-out of Aβ toxicity. For example, transgenic worms with pan-neuronal Aβ expression have defects is associative learning (Dosanjh et al. 2009), while transgenic worms with constitutive muscle-specific expression show a progressive, age-dependent paralysis phenotype (Link, 1995; Cohen et al. 2006). One particularly useful C. elegans model employs a temperature-sensitive mutation in the mRNA surveillance system to engineer temperature-inducible muscle expression of an Aβ transgene, resulting in a reproducible paralysis phenotype upon temperature upshift (Link et al. 2003). Treatments that counter Aβ toxicity in this model [e.g., expression of a protective transgene (Hassan et al. 2009) or exposure to Ginkgo biloba extracts (Wu et al. 2006)] reproducibly alter the rate of paralysis induced by temperature upshift of these transgenic worms. Here we describe our protocol for measuring the rate of paralysis in this transgenic C. elegans model, with particular attention to experimental variables that can influence this measurement.
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spelling pubmed-31856442011-10-06 Assaying β-amyloid Toxicity using a Transgenic C. elegans Model Dostal, Vishantie Link, Christopher D. J Vis Exp Neuroscience Accumulation of the β-amyloid peptide (Aβ) is generally believed to be central to the induction of Alzheimer's disease, but the relevant mechanism(s) of toxicity are still unclear. Aβ is also deposited intramuscularly in Inclusion Body Myositis, a severe human myopathy. The intensely studied nematode worm Caenorhabditis elegans can be transgenically engineered to express human Aβ. Depending on the tissue or timing of Aβ expression, transgenic worms can have readily measurable phenotypes that serve as a read-out of Aβ toxicity. For example, transgenic worms with pan-neuronal Aβ expression have defects is associative learning (Dosanjh et al. 2009), while transgenic worms with constitutive muscle-specific expression show a progressive, age-dependent paralysis phenotype (Link, 1995; Cohen et al. 2006). One particularly useful C. elegans model employs a temperature-sensitive mutation in the mRNA surveillance system to engineer temperature-inducible muscle expression of an Aβ transgene, resulting in a reproducible paralysis phenotype upon temperature upshift (Link et al. 2003). Treatments that counter Aβ toxicity in this model [e.g., expression of a protective transgene (Hassan et al. 2009) or exposure to Ginkgo biloba extracts (Wu et al. 2006)] reproducibly alter the rate of paralysis induced by temperature upshift of these transgenic worms. Here we describe our protocol for measuring the rate of paralysis in this transgenic C. elegans model, with particular attention to experimental variables that can influence this measurement. MyJove Corporation 2010-10-09 /pmc/articles/PMC3185644/ /pubmed/20972410 http://dx.doi.org/10.3791/2252 Text en Copyright © 2010, Journal of Visualized Experiments http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visithttp://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Neuroscience
Dostal, Vishantie
Link, Christopher D.
Assaying β-amyloid Toxicity using a Transgenic C. elegans Model
title Assaying β-amyloid Toxicity using a Transgenic C. elegans Model
title_full Assaying β-amyloid Toxicity using a Transgenic C. elegans Model
title_fullStr Assaying β-amyloid Toxicity using a Transgenic C. elegans Model
title_full_unstemmed Assaying β-amyloid Toxicity using a Transgenic C. elegans Model
title_short Assaying β-amyloid Toxicity using a Transgenic C. elegans Model
title_sort assaying β-amyloid toxicity using a transgenic c. elegans model
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185644/
https://www.ncbi.nlm.nih.gov/pubmed/20972410
http://dx.doi.org/10.3791/2252
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