TY - JOUR
T1 - Large animal models of huntington's disease
T2 - What we have learned and where we need to go next
AU - Howland, David
AU - Ellederova, Zdenka
AU - Aronin, Neil
AU - Fernau, Deborah
AU - Gallagher, Jill
AU - Taylor, Amanda
AU - Hennebold, Jon
AU - Weiss, Alison R.
AU - Gray-Edwards, Heather
AU - McBride, Jodi
N1 - Publisher Copyright:
© 2020-IOS Press and the authors. All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Minipigs
KW - nonhuman primates
KW - sheep
KW - therapeutics
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U2 - 10.3233/JHD-200425
DO - 10.3233/JHD-200425
M3 - Review article
C2 - 32925082
AN - SCOPUS:85092944595
SN - 1879-6397
VL - 9
SP - 201
EP - 216
JO - Journal of Huntington's disease
JF - Journal of Huntington's disease
IS - 3
ER -