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Dis Model Mech. 2019 Nov 8. pii: dmm.041293. doi: 10.1242/dmm.041293. [Epub ahead of print]

Longitudinal study revealed motor, cognitive and behavioral decline in transgenic minipig model of Huntington's disease.

Author information

1
Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic.
2
Department of Cell Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
3
Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic.
4
Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
5
Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic ellederova@iapg.cas.cz juhas@iapg.cas.cz.

Abstract

Huntington's disease (HD) is an inherited devastating neurodegenerative disease with no cure up to date. Several therapeutic treatments for HD are in development, nevertheless their safety, tolerability and efficacy need to be tested before translation to bedside. The monogenetic nature of this disorder enabled generation of transgenic animal models carrying mutant huntingtin gene (mHTT) causing HD. Large animal model reflecting disease progression in humans would be beneficial for testing the potential therapeutic approaches. Progression of motor, cognitive and behavioral phenotype was monitored in transgenic Huntington's disease minipigs (TgHD) expressing N-terminal part of human mHTT. New tests were established to investigate a physical activity by telemetry, and to explore stress induced behavior and cognitive changes in minipigs. The longitudinal study revealed significant differences in the 6 - 8 year-old TgHD animals compared to WT controls in majority of the tests. The telemetric study showed remarkable increase of physical activity of 4.6 - 6.5 year-old TgHD boars during the lunch time as well as in the afternoon. The present phenotypic study showed progression of the disease in adult TgHD minipigs and therefore this model can be suitable for longstanding preclinical studies.

KEYWORDS:

Cognitive and behavioral studies; Huntington's disease; Large animal model; Motor; Phenotyping

PMID:
31704691
DOI:
10.1242/dmm.041293
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