Motor behavioural tests for phenotype evaluation of mouse models of ataxia: the case of Marinesco-Sjögren Syndrome

Abstract

Ataxias are a clinically relevant group of neurological diseases characterized by impaired motor coordination that affects both static and dynamic control of body movements. Among the autosomal recessive ataxias there is Marinesco-Sjogren syndrome (MSS). The main clinical signs of MSS are incoordination with cerebellar atrophy, and myopathy associated to hypotonia. Mouse models of MSS (e.g. woozy mouse) closely mimic human pathology and are widely used to study this disease. In fact, the woozy mouse was helpful in understanding that molecular alteration occurs before clinical signs. To data, several motor behavioural tests have been developed including rotarod, beam walking, and grip-strength. Some of these tests were effective to reveal MSS ataxia only at specific stages of the disease. To achieve these results, it is important to apply the most appropriate motor behavioural tests that are able to sensitively assess the specific phenotype. However, the administration of additional motor tests would be useful to better define the coordination and motor problems in MSS. Cognitive tests should also be considered to examine whether the woozy model has mental retardation. In conclusion, motor and cognitive tests are essential for the assessment of disease stage and future therapies in ataxias, including MSS.