Gait parameters as tools for analyzing phenotypic alterations of a mouse model of Charcot-Marie-Tooth disease.

ABSTRACT

Charcot-Marie-Tooth disease (CMT), a genetically heterogeneous group of diseases in the peripheral nervous system, is characterized by progressive and symmetrical distal weakness resulting in gait abnormality. The necessity of the diagnostic and prognostic biomarkers has been raised for both basic research and clinical practice in CMT. Since biomarkers for animal study of CMT are limited, we evaluated the feasibility of gait parameters as tool for measuring disease phenotype of CMT mouse model. Using a Trembler-J (Tr-J) mouse, a CMT type 1 (CMT1) mouse model, we analyzed kinematic parameters such as angles of hip, knee and ankle (sagittal plane), and spatial parameters including step width and stride length (transverse plane). Regarding of kinematic parameters, Tr-J mice exhibited less plantarflexed ankle during the swing phase and more dorsiflexed ankle at the terminal stance compared to control mice. The range of motion in ankle angle of Tr-J mice was significantly greater than that of control mice. In spatial parameter, Tr-J mice exhibited wider step width compared to control mice. These results are similar to previously reported gait patterns of CMT1 patients. In comparison with other markers such as nerve conduction study and rotarod test, gait parameters dynamically reflected the disease progression of CMT1 mice. Therefore, these data imply that gait parameters can be used as useful tools to analyzed the disease phenotype and progression during preclinical study of peripheral neuropathy such as CMT.