Development of mAb-based polyglutamine-dependent and polyglutamine length-independent huntingtin quantification assays with cross-site validation.
Huntington's disease (HD) is caused by an expansion of the CAG trinucleotide repeat domain in the huntingtin gene that results in expression of a mutant huntingtin protein (mHTT) containing an expanded polyglutamine tract in the amino terminus. A number of therapeutic approaches that aim to red...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0266812 |
| _version_ | 1811333608015659008 |
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| author | David F Fischer Sipke Dijkstra Kimberly Lo Johnny Suijker Ana C P Correia Patricia Naud Martin Poirier Michela A Tessari Ivette Boogaard Geraldine Flynn Mijke Visser Marieke B A C Lamers George McAllister Ignacio Munoz-Sanjuan Douglas Macdonald |
| author_facet | David F Fischer Sipke Dijkstra Kimberly Lo Johnny Suijker Ana C P Correia Patricia Naud Martin Poirier Michela A Tessari Ivette Boogaard Geraldine Flynn Mijke Visser Marieke B A C Lamers George McAllister Ignacio Munoz-Sanjuan Douglas Macdonald |
| author_sort | David F Fischer |
| collection | DOAJ |
| description | Huntington's disease (HD) is caused by an expansion of the CAG trinucleotide repeat domain in the huntingtin gene that results in expression of a mutant huntingtin protein (mHTT) containing an expanded polyglutamine tract in the amino terminus. A number of therapeutic approaches that aim to reduce mHTT expression either locally in the CNS or systemically are in clinical development. We have previously described sensitive and selective assays that measure human HTT proteins either in a polyglutamine-independent (detecting both mutant expanded and non-expanded proteins) or in a polyglutamine length-dependent manner (detecting the disease-causing polyglutamine repeats) on the electrochemiluminescence Meso Scale Discovery detection platform. These original assays relied upon polyclonal antibodies. To ensure an accessible and sustainable resource for the HD field, we developed similar assays employing monoclonal antibodies. We demonstrate that these assays have equivalent sensitivity compared to our previous assays through the evaluation of cellular and animal model systems, as well as HD patient biosamples. We also demonstrate cross-site validation of these assays, allowing direct comparison of studies performed in geographically distinct laboratories. |
| first_indexed | 2024-04-13T16:55:24Z |
| format | Article |
| id | doaj.art-d40329dcbdbd4ce6b214f506ecdfe85c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T16:55:24Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d40329dcbdbd4ce6b214f506ecdfe85c2022-12-22T02:38:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01174e026681210.1371/journal.pone.0266812Development of mAb-based polyglutamine-dependent and polyglutamine length-independent huntingtin quantification assays with cross-site validation.David F FischerSipke DijkstraKimberly LoJohnny SuijkerAna C P CorreiaPatricia NaudMartin PoirierMichela A TessariIvette BoogaardGeraldine FlynnMijke VisserMarieke B A C LamersGeorge McAllisterIgnacio Munoz-SanjuanDouglas MacdonaldHuntington's disease (HD) is caused by an expansion of the CAG trinucleotide repeat domain in the huntingtin gene that results in expression of a mutant huntingtin protein (mHTT) containing an expanded polyglutamine tract in the amino terminus. A number of therapeutic approaches that aim to reduce mHTT expression either locally in the CNS or systemically are in clinical development. We have previously described sensitive and selective assays that measure human HTT proteins either in a polyglutamine-independent (detecting both mutant expanded and non-expanded proteins) or in a polyglutamine length-dependent manner (detecting the disease-causing polyglutamine repeats) on the electrochemiluminescence Meso Scale Discovery detection platform. These original assays relied upon polyclonal antibodies. To ensure an accessible and sustainable resource for the HD field, we developed similar assays employing monoclonal antibodies. We demonstrate that these assays have equivalent sensitivity compared to our previous assays through the evaluation of cellular and animal model systems, as well as HD patient biosamples. We also demonstrate cross-site validation of these assays, allowing direct comparison of studies performed in geographically distinct laboratories.https://doi.org/10.1371/journal.pone.0266812 |
| spellingShingle | David F Fischer Sipke Dijkstra Kimberly Lo Johnny Suijker Ana C P Correia Patricia Naud Martin Poirier Michela A Tessari Ivette Boogaard Geraldine Flynn Mijke Visser Marieke B A C Lamers George McAllister Ignacio Munoz-Sanjuan Douglas Macdonald Development of mAb-based polyglutamine-dependent and polyglutamine length-independent huntingtin quantification assays with cross-site validation. PLoS ONE |
| title | Development of mAb-based polyglutamine-dependent and polyglutamine length-independent huntingtin quantification assays with cross-site validation. |
| title_full | Development of mAb-based polyglutamine-dependent and polyglutamine length-independent huntingtin quantification assays with cross-site validation. |
| title_fullStr | Development of mAb-based polyglutamine-dependent and polyglutamine length-independent huntingtin quantification assays with cross-site validation. |
| title_full_unstemmed | Development of mAb-based polyglutamine-dependent and polyglutamine length-independent huntingtin quantification assays with cross-site validation. |
| title_short | Development of mAb-based polyglutamine-dependent and polyglutamine length-independent huntingtin quantification assays with cross-site validation. |
| title_sort | development of mab based polyglutamine dependent and polyglutamine length independent huntingtin quantification assays with cross site validation |
| url | https://doi.org/10.1371/journal.pone.0266812 |
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