Rieke Lorena, Schubert Robin, Matheis Tamara, Muratori Lisa M, Motlik Jan, Schramke Sarah, Fels Michaela, Kemper Nicole, Schuldenzucker Verena, Reilmann Ralf
George-Huntington-Institute, Technology Park Muenster, Muenster, Germany.
Institute for Animal Hygiene, Animal Welfare and Farm Animal Behaviour, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
J Huntingtons Dis. 2018;7(3):269-278. doi: 10.3233/JHD-170284.
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.
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.
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.
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.
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.
如转基因亨廷顿病（HD）小型猪等大型动物模型已被提议用于提高临床前研究中转译的可靠性以及安全性、有效性和耐受性评估。小型猪具有与人类高度的基因同源性和可比的脑结构。此外，可以在小型猪中探索成功应用于人类的行为评估，以在临床前和临床研究中建立相似的终点。最近，语音和言语产生分析已被用于对HD患者进行特征描述。
本研究的目的是调查发声是否也可作为亨廷顿病转基因小型猪（tgHD）表型分析的可行标志物，以及与野生型（wt）小型猪相比，tgHD小型猪在这方面是否有变化。
在进行行为测试时，对一组14只tgHD小型猪和18只wt小型猪的发声发生率进行评估。使用Fisher精确检验进行组间比较，使用McNemar检验分析tgHD和wt小型猪每次测试期间的差异。
在小型猪的表型评估过程中可以很容易地记录发声情况。在tgHD和wt小型猪之间检测到不同行为条件下发声发生率的差异。在1.5年的时间内可检测到基因型对发声的影响。
发声可能是亨廷顿基因转基因小型猪表型分析的可行标志物。发声记录提供了一个非侵入性的机会来捕捉潜在的疾病迹象，并探索包括疾病表现年龄在内的表型发展。
