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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MyJove Corporation
2010
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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. |
format | Online Article Text |
id | pubmed-3185644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | MyJove Corporation |
record_format | MEDLINE/PubMed |
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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