The cochlear morphology alteration and hearing loss in Cep250 knockout mice

Abstract

Background: Usher syndrome is a genetic disorder characterized by sensorineural hearing loss, progressive vision loss, and in some cases, vestibular dysfunction. It is the most common cause of combined deafness and blindness. Cep250 is a candidate gene for atypical Usher syndrome. This study explores inner ear morphological and auditory functional changes in atypical Usher syndrome using a Cep250^−/− mouse model. Methods: We constructed the Cep250^−/− mice using the CRISPR/Cas9 technology, and analyzed scRNA-seq data derived from studying Cep250 expression in the cochlea of normal mice at different stages. Auditory brainstem responses (ABRs) were applied to wild-type, heterozygous and homozygous Cep250^−/− mice at about P30 to P60 to assess the general function of the inner ear. The swimming test was used to examine the vestibular function of the inner ear. Immunofluorescent staining was applied to observe hair cell morphology and count hair cell numbers. Results: We demonstrate that Cep250^−/− mice exhibit impaired hearing function, particularly in high-frequency ranges, whereas their vestibular function remains unaffected. Immunofluorescence staining reveals a significant reduction in the number of cochlear hair cells in Cep250^−/− mice, confirming the association between Cep250 gene mutation and hearing function loss. Heterozygous mice show no significant changes in hearing, indicating that a single allele mutation in Cep250 is insufficient to affect normal Cep250 expression levels. Conclusion: Our findings contribute to a deeper understanding of atypical Usher syndrome and may guide future research and therapeutic strategies for this condition.