The 133-kDa N-terminal region of myosin XVa is critical for normal structure and function of auditory and hair cells.

BACKGROUND

is a commonly implicated gene in severe to profound sensorineural hearing loss. Numerous studies have identified mutations in in humans, analyzed their presence and co-segregation, and predicted their pathogenicity using software tools. However, few have investigated the pathogenic mechanisms of these mutations using mouse models. In a prior study, we identified the c.2482 C > T mutation as a potential causative gene for deafness in a Uygur family from Xinjiang. To further explore the pathogenicity and mechanisms of this mutation, we constructed a mouse model harboring the c.2455A > T mutation. This study demonstrates that mice with the c.2455A > T spot knock-in exhibit the abnormal hair cell morphology, dysfunction, and hearing loss phenotype observed in humans.

OBJECTIVES

To investigate the pathogenic mechanism of deafness caused by c.2482C > T mutation.

MATERIAL AND METHODS

To assess the impact of the MYO15A mutation on hair cell morphology and function, mice underwent audiological tests, quantitative real-time PCR, scanning electron microscopy, immunofluorescence, and Western blot analysis.

RESULTS

The p.Arg819* mutation located in the N-terminal domain of showed marked differences in hair cell morphology and function between homozygous mutant mice and normal controls. Notably, the homozygous mutant mice retained residual hearing up to approximately five weeks of age.

CONCLUSIONS AND SIGNIFICANCE

Our findings confirm that c.2455A > T spot knock-in mice replicate the abnormal hair cell morphology and dysfunction, as well as the hearing loss phenotype. Additionally, our results indicate that the novel c.2482C > T variant in the gene can cause inner ear hair cell dysfunction and audiological disorders in this family.