Progressive auditory neuropathy (AN) in the P0-deficient mouse model

Introduction:

Patients with AN have a progressive hearing loss characterized by a reduced understanding of speech. This is based on a dysfunction of the nerve conduction of the cochlear nerve and the hair cell synapses. This disease has also been observed in patients with polyneuropathy in underlying neurological disorders such as Charcot-Marie-Tooth disease. The protein zero (P0)-deficient mouse is an established model of this disease associated by dysmyelination and peripheral axon loss.

Methods:

For the evaluation of the hearing, P0 -/- and C57Bl6 wild-type mice were examined in the age of 3 – 12 months. Frequency-specific brainstem audiometry (ABR) and the distortion product of otoacoustic emissions (DPOAE) of these animals were measured. These results were histologically correlated with immunohistochemical staining of the cochleae and electron micrographs of the auditory nerves.

Results:

From 6 months of age, significantly elevated ABR thresholds were seen in the P0 -/- animals, while the DPOAE were unchanged by comparison. Histologically, the Organs of Corti showed no structural differences in contrast to the wild type, while the peripheral parts of the cochlear nerves showed signs of dysmyelination and reduced axonal diameters.

Discussion:

In summary, in the P0-deficient mouse model auditory-electrophysiological evidence of a progressive auditory neuropathy could be demonstrated. Morphological and physiological similarities were found to the known changes in the disease in humans. This mouse model can, therefore, be used in the future for the further investigation of auditory neuropathy and the development of new therapeutic approaches.

Publication History

Publication Date:
23 April 2019 (online)