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Large Animal Models of Huntington’s Disease: What We Have Learned and Where We Need to Go Next
Genetically modified rodent models of Huntington’s disease (HD) have been especially valuable to our understanding of HD pathology and the mechanisms by which the mutant HTT gene alters physiology. However, due to inherent differences in genetics, neuroanatomy, neurocircuitry and neurophysiology, an...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597371/ https://www.ncbi.nlm.nih.gov/pubmed/32925082 http://dx.doi.org/10.3233/JHD-200425 |
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author | Howland, David Ellederova, Zdenka Aronin, Neil Fernau, Deborah Gallagher, Jill Taylor, Amanda Hennebold, Jon Weiss, Alison R. Gray-Edwards, Heather McBride, Jodi |
author_facet | Howland, David Ellederova, Zdenka Aronin, Neil Fernau, Deborah Gallagher, Jill Taylor, Amanda Hennebold, Jon Weiss, Alison R. Gray-Edwards, Heather McBride, Jodi |
author_sort | Howland, David |
collection | PubMed |
description | Genetically modified rodent models of Huntington’s disease (HD) have been especially valuable to our understanding of HD pathology and the mechanisms by which the mutant HTT gene alters physiology. However, due to inherent differences in genetics, neuroanatomy, neurocircuitry and neurophysiology, animal models do not always faithfully or fully recapitulate human disease features or adequately predict a clinical response to treatment. Therefore, conducting translational studies of candidate HD therapeutics only in a single species (i.e. mouse disease models) may not be sufficient. Large animal models of HD have been shown to be valuable to the HD research community and the expectation is that the need for translational studies that span rodent and large animal models will grow. Here, we review the large animal models of HD that have been created to date, with specific commentary on differences between the models, the strengths and disadvantages of each, and how we can advance useful models to study disease pathophysiology, biomarker development and evaluation of promising therapeutics. |
format | Online Article Text |
id | pubmed-7597371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-75973712020-10-30 Large Animal Models of Huntington’s Disease: What We Have Learned and Where We Need to Go Next Howland, David Ellederova, Zdenka Aronin, Neil Fernau, Deborah Gallagher, Jill Taylor, Amanda Hennebold, Jon Weiss, Alison R. Gray-Edwards, Heather McBride, Jodi J Huntingtons Dis Review Genetically modified rodent models of Huntington’s disease (HD) have been especially valuable to our understanding of HD pathology and the mechanisms by which the mutant HTT gene alters physiology. However, due to inherent differences in genetics, neuroanatomy, neurocircuitry and neurophysiology, animal models do not always faithfully or fully recapitulate human disease features or adequately predict a clinical response to treatment. Therefore, conducting translational studies of candidate HD therapeutics only in a single species (i.e. mouse disease models) may not be sufficient. Large animal models of HD have been shown to be valuable to the HD research community and the expectation is that the need for translational studies that span rodent and large animal models will grow. Here, we review the large animal models of HD that have been created to date, with specific commentary on differences between the models, the strengths and disadvantages of each, and how we can advance useful models to study disease pathophysiology, biomarker development and evaluation of promising therapeutics. IOS Press 2020-10-08 /pmc/articles/PMC7597371/ /pubmed/32925082 http://dx.doi.org/10.3233/JHD-200425 Text en © 2020 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Howland, David Ellederova, Zdenka Aronin, Neil Fernau, Deborah Gallagher, Jill Taylor, Amanda Hennebold, Jon Weiss, Alison R. Gray-Edwards, Heather McBride, Jodi Large Animal Models of Huntington’s Disease: What We Have Learned and Where We Need to Go Next |
title | Large Animal Models of Huntington’s Disease: What We Have Learned and Where We Need to Go Next |
title_full | Large Animal Models of Huntington’s Disease: What We Have Learned and Where We Need to Go Next |
title_fullStr | Large Animal Models of Huntington’s Disease: What We Have Learned and Where We Need to Go Next |
title_full_unstemmed | Large Animal Models of Huntington’s Disease: What We Have Learned and Where We Need to Go Next |
title_short | Large Animal Models of Huntington’s Disease: What We Have Learned and Where We Need to Go Next |
title_sort | large animal models of huntington’s disease: what we have learned and where we need to go next |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597371/ https://www.ncbi.nlm.nih.gov/pubmed/32925082 http://dx.doi.org/10.3233/JHD-200425 |
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