Training and aging modulate the loss-of-balance phenotype observed in a new ENU-induced allele of Otopetrin1.

BACKGROUND INFORMATION: The sensing of head movement in mammals depends upon the vestibular endorgan of the inner ear, a complex structure made up of the semicircular canals and otoliths. Due to the similarity between the human and mouse vestibular apparatus, the analysis of mutant mouse is a valuable strategy aiming to identify genes involved in the control of balance and movement.
RESULTS: In the course of a genome-wide chemical-mutagenesis programme, we isolated a recessive mutation, named ied (inner ear defect), which induced a severe loss-of-balance. A detailed phenotypic analysis of the mutant mice demonstrates that the balance impairment does not affect the motor activity and can be rescued, in part, by training, despite a complete agenesis of otoconia in the utricule and the saccule of the inner ear. Molecular characterization of the ied mutation revealed a transversion that affects the splicing of the second exon of the Otopetrin1 gene located on mouse chromosome 5. The consequence of such a mutation leads to a disruption of the transcription of the gene.
CONCLUSIONS: The identification of the ied knock-down allele strengthens the role of the Otopetrin1 in the sensing of balance. Moreover, the rescue of the ied mutant phenotype in specific behavioural tasks confirmed that other sensory inputs or neural plasticity can compensate, to some extent, for the loss-of-balance. In the future, the ied mutant mice might be helpful to study the genetic control of the compensation strategies developed by organisms to counteract balance defects.