Vocalisation as a Viable Assessment for Phenotyping Minipigs Transgenic for the Huntington Gene?

Article type: Research Article

Authors: Rieke, Lorena^{a; b} | Schubert, Robin^a | Matheis, Tamara^{a; b} | Muratori, Lisa M.^{a; c} | Motlik, Jan^d | Schramke, Sarah^a | Fels, Michaela^b | Kemper, Nicole^b | Schuldenzucker, Verena^{a; e} | Reilmann, Ralf^{a; f; g; *}

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 Physical Therapy, School of Health Technology and Management, Stony Brook University, Stony Brook, NY, USA | [d] Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, v.v.i., AS CR, Libechov, Czech Republic | [e] Institute of Zoology, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany | [f] Department of Radiology, Universitaetsklinikum Muenster, Albert-Schweitzer Campus, Muenster, Germany | [g] 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 Muenster, Deilmann Building, Johann-Krane-Weg 27, 48149 Muenster, Germany. Tel.: +49 251 788 788 11; Fax: +49 251 788 788 88; E-mail: [email protected].

Abstract: Background:Large animal models, such as the transgenic (tg) Huntington disease (HD) minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. Objective:The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping minipigs transgenic for Huntington’s disease (tgHD) and whether tgHD minipigs reveal changes in this domain compared to wildtype (wt) minipigs. Methods:While conducting behavioural testing, incidence of vocalisation was assessed for a cohort of 14 tgHD and 18 wt minipigs. Statistical analyses were performed using Fisher’s Exact Test for group comparisons and McNemar’s Test for intra-visit differences between tgHD and wt minipigs. Results:Vocalisation can easily be documented during phenotyping assessments of minipigs. Differences in vocalisation incidences across behavioural conditions were detected between tgHD and wt minipigs. Influence of the genotype on vocalisation was detectable during a period of 1.5 years. Conclusion:Vocalisation may be a viable marker for phenotyping minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation.

Keywords: Large animal model, transgenic, minipig, vocalisation, phenotyping, preclinical

DOI: 10.3233/JHD-170284

Journal: Journal of Huntington's Disease, vol. 7, no. 3, pp. 269-278, 2018