Severe vestibular and auditory impairment in three alleles of Ames waltzer(av) mice

The genetic and physiological characterization of circling, hearing-impaire d mouse mutants has greatly facilitated our understanding of non-syndromic sensorineural deafness, the most common form of hereditary human hearing lo ss. Here we report the first phenotypic characterization of three alleles o f Ames waltzer (av). Neither electrical potentials (auditory brainstem resp onse) nor behavioral responses to sound could be evoked in any of the three alleles at any age or frequency. However, the endocochlear potential was f ound to be normal, indicating that the primary pathology is not in the stri a vascularis. To determine the earliest changes and help identify the prima ry causes of deafness in av, we performed morphological studies in 15-16 da y old mutants, just prior to the maturation of the cochlea. Although av(2J) is slightly more affected than the other two alleles, our studies show a h igh similarity between all three alleles. The first detectable changes are observed in the stereocilia and cytoplasm of hair cells, and in the cellula r shape and microvilli of supporting cells. These changes are followed by d egeneration of the cochlear and vestibular neuroepithelium. (C) 2001 Elsevi er Science B.V. All rights reserved.