Activity Behaviour of Minipigs Transgenic for the Huntington Gene

Article type: Research Article

Authors: Rieke, Lorena^{a; b} | Fels, Michaela^b | Schubert, Robin^a | Habbel, Benjamin^a | Matheis, Tamara^{a; b} | Schuldenzucker, Verena^a | Kemper, Nicole^b | Reilmann, Ralf^{a; c; d; *}

Affiliations: [a] George-Huntington-Institute, Technology Park Muenster, Muenster, Germany | [b] Institute for Animal Hygiene, Animal Welfare and Farm Animal Behaviour, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany | [c] Department of Radiology, Universitaetsklinikum Muenster, Muenster, Germany | [d] Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany

Correspondence: [*] Correspondence to: Ralf Reilmann, MD, PhD, FAAN, Founding Director, George-Huntington-Institute, Technology-Park Muenste, Deilmann Building, Johann-Krane-Weg 27, D-48149 Muenster, Germany. Coordinator: +49 251 788 788 0; Office: +49 251 788 788 11; Fax: +49 251 788 788 88; E-mail: [email protected].

Abstract: Background:To increase the reliability of translating preclinical findings to humans, large animal models, such as the transgenic (tg) Libechov minipig, were established. As minipigs possess high genetic homology with humans and have similarities in anatomy, physiology and metabolism to humans, they are considered for studying neurodegenerative diseases longitudinally. Recently, sleep abnormalities and changes in circadian rhythm in Huntington’s disease (HD) patients were acknowledged to present one of the early symptoms in HD. Objective:The aim of the present study was to explore the activity behaviour of Libechov minipigs and to investigate whether tgHD and wildtype (wt) minipigs exhibit differences in activity behaviour. Furthermore, it was investigated whether activity assessments may serve as reliable endpoints for phenotyping minipigs transgenic for the Huntington gene. Methods:Activity behaviour of minipigs was studied by video recording the stables twice a week over a total study period of five weeks for a cohort of five tgHD minipigs and five wt minipigs. Statistical analysis was performed using the linear mixed model. Once a week, the distances covered by two minipigs in focus (tgHD, wt) were measured using the VideoMotionTracker® software. Results:Libechov minipigs showed a biphasic pattern of activity, spending most of the time inactive or grubbing in litter. Differences in activity behaviour (rooting, resting and standing) were detected between wt and tgHD minipigs. The influence of the genotype on behavioural patterns was observed during circadian monitoring. TgHD minipigs covered longer distances on average and during every 24 h observation period than wt minipigs. Conclusion:Activity behaviour may be a viable marker for phenotyping minipigs transgenic for the Huntington gene. Video recordings of behavioural patterns provide a non-invasive opportunity to capture potential disease signs. Phenotypic progression including the age of disease manifestation may be explored by documentation of circadian characteristics.

Keywords: Large animal model, transgenic, minipig, activity, behaviour, phenotyping

DOI: 10.3233/JHD-180325

Journal: Journal of Huntington's Disease, vol. 8, no. 1, pp. 23-31, 2019