Genetically induced inner ear degeneration. A structural and functional study.

The jerker mouse mutant has an autosomal recessive mutation, which in homozygotes results in early postnatal degeneration of the sensory epithelia in both the cochlea and vestibulum. An age-related consecutive functional and morphological analysis of the cochlea has been performed in homozygote (je/je) and heterozygote (je/+) jerker mice. Cochlear function was determined with auditory brainstem response (ABR) technique. Heterozygotes were regularly tested to a final age of 12 months. With increasing age they displayed ABR threshold shifts which were of about the same magnitude in the whole frequency range tested (2-31.5 kHz) but extremely variable in individual animals. From homozygote jerker mice no ABR could be elicited. There was a similar morphologic pattern of cochlear degeneration in both homozygote and heterozygote jerker mice affecting primarily the stereocilia and cuticular plate in both outer and inner hair cells. In homozygotes these changes were found in very young animals but in heterozygotes they did not become evident until later in life. All parts of the cochlea became simultaneously affected, that means there was no topographical gradient in the pathological course. The ABR thresholds in 12 months old heterozygotes were correlated semiquantitatively to hair cell pathology in the cochlea. The functional and morphological changes in heterozygotes probably reflect a random influence of the jerker gene vis-à-vis the wild type of gene.