[The expression of P19ink4d in the pathogenesis and development of hearing loss]

Objective: This study aimed to investigate the P19ink4d expression in cochlea of mice model with noise induced hearing loss and the role of P19ink4d in the degeneration of inner ear cells. It also searched for P19ink4d gene alterations in patients with profound sensorineural deafness.Method: CBA/J mice were exposed to broad band noise at 101 dB SPL for 2 hours, auditory brainstem response (ABR) were examined to confirm noise lead to the permanent threshold shift. Immunohistochemical staining, Western blotting, and real-time polymerase chain reaction (PCR) were performed on cochlear tissues, to elucidate changes in P19ink4d expression in mice after noise exposure. For clinical evaluation, 400 children from unrelated families with severe or profound sensorineural hearing loss (SNHL) were recruited, genomic DNA was obtained from the patients and was subjected to DNA microarray to screen mutations in 4 most common genes. The sample that carried none of the common mutant alleles were subjected to PCR and sequenced to detect mutations in P19ink4d gene.Result: The ABR threshold shift of mice in the experimental group significantly increased after noise exposure and was higher than that in the null-noise group. The ABR of 1 day post noise was least among experimental groups and there is no statistical different between ABR of 7 days and 14 days post noise. The missing of outer hair cells occurred after noise exposure, while the inner hair cells hardly miss. It was found that the P19ink4d expression increased significantly in the inner ear cells 3 hours after noise exposure, then recovered in 24 hours. Western blot indicated that the amount of P19ink4d increased transitorily 3-6 h after the noise. However, no mutation existed within the coding exons of P19ink4d in the patients with profound sensorineural deafness.Conclusion: The results support the concept that P19ink4d may play an important role in the pathogenesis and development of noise induced hearing loss.