Phenotypic evaluation of a childhood-onset parkinsonism-dystonia mouse model with inherent postural abnormalities.

Abstract

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 Slc39a14mice 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 Slc39a14mice 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 Slc39a14model presents a complex pathological motor phenotype relevant to the complexity of phenotypes identified in childhood-onset parkinsonism-dystonia.