Mouse models that replicate facets of human neurological diseases are often used at the pre-clinical stage to better understand the underlying mechanisms of a disease and test the target engagement of potential therapeutic interventions. We recently characterized a mouse model of childhood-onset parkinsonism-dystonia, a disease caused by a homozygous loss-of-function mutation in the SLC39A14 gene. The disease manifests itself phenotypically by impairments in locomotor behaviour and postural abnormalities. Our initial characterization of the model revealed that the Slc39a14^−/− mice showed altered Mn homeostasis and compromised locomotor performance in vertical pole-descending, horizontal beam-traversing, and rotarod tests (Jenkitkasemwong et al., 2018). However, some of the mice also displayed torticollis and Straub tail. In this study, we investigated whether these postural abnormalities affected the performance in the above motility tests and consequently, biased and compromised the external validity of reported abnormal locomotor profiles. Our analyses showed that the Slc39a14^−/− mice displaying torticollis and/or Straub tail had tests scores comparable to scores of their counterparts that never displayed these postural abnormalities. The z-score general index of performance revealed that the Slc39a14^−/− model presents a complex pathological motor phenotype relevant to the complexity of phenotypes identified in childhood-onset parkinsonism-dystonia.

复制人类神经疾病方面的小鼠模型通常用于临床前阶段，以更好地了解疾病的潜在机制并测试潜在治疗干预的目标参与。我们最近对儿童期发病的帕金森综合征-肌张力障碍小鼠模型进行了表征，这是一种由SLC39A14基因纯合功能丧失突变引起的疾病。该疾病的表型表现为运动行为受损和姿势异常。我们对该模型的初步表征表明Slc39a14 ^-/-小鼠在垂直极降、水平横梁和旋转杆测试中显示出改变的锰稳态和运动性能受损（Jenkitkasemwong 等人，2018 年）。然而，一些小鼠也表现出斜颈和 Straub 尾。在这项研究中，我们调查了这些姿势异常是否影响了上述运动测试的表现，并因此偏向和损害了报告的异常运动特征的外部有效性。我们的分析表明，显示斜颈和/或 Straub 尾的Slc39a14 ^-/-小鼠的测试分数与从未表现出这些姿势异常的对应物的分数相当。z-score 一般性能指标显示Slc39a14 ^-/- 模型呈现了一种复杂的病理运动表型，与在儿童期发作的帕金森综合征-肌张力障碍中确定的表型的复杂性相关。