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Transgenic Animal Models of Huntington’s Disease

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Book cover Molecular and Functional Models in Neuropsychiatry

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 7))

Abstract

Huntington’s disease (HD) is a devastating neurodegenerative disorder that currently has no cure. In order to develop effective treatment, an understanding of HD pathogenesis and the evaluation of therapeutic efficacy of novel medications with the aid of animal models are critical steps. Transgenic animals sharing similar genetic defects that lead to HD have provided important discoveries in HD mechanisms that cell models are not able to replicate, which include psychiatric impairment, cognitive behavioral impact, and motor functions. Although transgenic HD rodent models have been widely used in HD research, it is clear that an animal model with comparable physiology to man, similar genetic defects that lead to HD, and the ability to develop similar cognitive and behavioral impairments is critical for explaining HD pathogenesis and the development of cures. Compared to HD rodents, HD transgenic nonhuman primates have not only developed comparable neuropathology but also present HD clinical features such as rigidity, seizure, dystonia, bradykinesia, and chorea that no other animal model has been able to replicate. Distinctive degenerating neurons and the accumulation of neuropil aggregates observed in HD monkey brain strongly support the hypothesis that the unique neuropathogenic events seen in HD monkey brain recapitulate HD in man. The latest development of transgenic HD primates has opened a new era of animal modeling that better represents human genetic disorders such as HD, which will accelerate the development of diagnostic tools and identifying novel biomarkers through longitudinal studies including gene expression and metabolite profiling, and noninvasive imaging. Furthermore, novel treatments with predictable efficacy in human patients can be developed using HD monkeys because of comparable neuropathology and clinical features.

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Acknowledgment

This work is supported by NCRR/NIH grant R24RR01882 and YNPRC is supported by NIH grants RR-00165.

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  1. Department of Physiology, National Cheng Kung University Medical College, 1, University Road, Tainan, 70101, Taiwan

    Shang-Hsun Yang

  2. Division of Neuroscience, Department of Human Genetics, Yerkes National Primate Research Center, Emory University School of Medicine, Rm.2212 Neuroscience Research Building, 954 Gatewood Road, N.E., Atlanta, GA, 30329, USA

    Anthony W. S. Chan

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Correspondence to Anthony W. S. Chan .

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  1. Global Medical Excellence Cluster (GMEC), King's College London, London, SE1 1UL, United Kingdom

    Jim J. Hagan

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Yang, SH., Chan, A.W.S. (2011). Transgenic Animal Models of Huntington’s Disease. In: Hagan, J. (eds) Molecular and Functional Models in Neuropsychiatry. Current Topics in Behavioral Neurosciences, vol 7. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2010_105

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