Shared and specific signatures of locomotor ataxia in mutant mice.

Abstract

Several spontaneous mouse mutants with deficits in motor coordination and associated cerebellar neuropathology have been described. Intriguingly, both visible gait alterations and neuroanatomical abnormalities throughout the brain differ across mutants. We previously used the LocoMouse system to quantify specific deficits in locomotor coordination in mildly ataxic <i>Purkinje cell degeneration</i> mice (<i>pcd;</i> Machado et al., 2015). Here, we analyze the locomotor behavior of severely ataxic <i>reeler</i> mutants and compare and contrast it with that of <i>pcd</i>. Despite clearly visible gait differences, direct comparison of locomotor kinematics and linear discriminant analysis reveal a surprisingly similar pattern of impairments in multijoint, interlimb, and whole-body coordination in the two mutants. These findings capture both shared and specific signatures of gait ataxia and provide a quantitative foundation for mapping specific locomotor impairments onto distinct neuropathologies in mice.