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.
- Klíčová slova
- Large animal model, minipig, phenotyping, preclinical, transgenic, vocalisation,
- MeSH
- časové faktory MeSH
- diskriminace (psychologie) MeSH
- fenotyp * MeSH
- geneticky modifikovaná zvířata * MeSH
- Huntingtonova nemoc * patofyziologie psychologie MeSH
- jazyk patofyziologie MeSH
- lidé MeSH
- longitudinální studie MeSH
- miniaturní prasata * MeSH
- modely nemocí na zvířatech * MeSH
- motorické dovednosti MeSH
- prasata MeSH
- protein huntingtin genetika metabolismus MeSH
- reverzní učení MeSH
- vnímání barev MeSH
- vokalizace zvířat * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- HTT protein, human MeSH Prohlížeč
- protein huntingtin MeSH