Mutational ataxia resulting from abnormal vestibular acquisition and processing is partially compensated for

Due to the multisensory input into the balance system, the loss of one input, such as an ear, can generally be compensated for. However, when a mismatch or incomplete loss of inputs occurs, the ability to compensate for the stimulus misrepresentation may be compromised. The inner ear and cerebellum are important input and processing centers for balance but no genetic models have been generated to assess balance or compensation in the abnormal development of both these organs/brain areas. Important to their formation is regulation of proliferation mediated by the proto-oncogene N-Myc. Conditional knockouts (CKOs) of N-Myc using Tg(Pax2-Cre) have a misshapen and smaller ear with a fused utricle, saccule, and cochlea and absent horizontal canal, aberrant cochlear and vestibular innervations, and a size reduction in the cerebellum. CKOs are viable with obvious behavioral deficits, including circling behavior and unstable gait. To test the degree of ataxia and possible compensation of vestibular defects in these mutant mice, we use the Noldus Catwalk System to assess the gait of Tg(Pax2-Cre) N-Myc CKOs over five months. N-Myc CKOs perform worse than control littermates, in particular, in step regularity. We show that disrupting one member of the Myc family during embryonic development coincides with a differential loss of function in the cochlea compared to the vestibular apparatus. In addition, we show that the distortion in the ear morphology combined with a reduction of the cerebellum, rather than a complete loss of the vestibular-cerebellar pathway, leads to partial behavioral compensation that remains unchanged over time.