The effect of the Arg1956Trp mutation in the IQ3 domain of MYO15A on stereocilia formation and hearing loss
In: Student Reports, Summer 2022, The Jackson Laboratory
Elli Hartig, predoctoral associate.
By 2030, it is predicted that 2.5 billion people around the world will live with hearing loss. One of the primary causes of hearing loss and deafness is irregular stereocilia formation within the hair cells of the inner ear. To better understand this cause of hearing loss and deafness in humans, we have studied hearing loss and deafness using a mouse model. In this study, we researched the Arg1940Trp (RW) mutation within the IQ3 light chain binding domain of the MYO15A protein, the motor protein responsible for transporting the cell elongation complex to stereocilia tips. We hypothesized that the mutation would alter the binding of the CETN2 light chain and MYO15A protein giving rise to irregular stereocilia and hearing impairments. This was tested by phenotyping mice with the RW mutation using Auditory Brainstem Response to obtain hearing thresholds and immunohistochemistry to visualize the stereocilia. MYO15A and CETN2 binding was researched using filopodia and immunoprecipitation assays. We found that the RW mutation correlated with hearing loss at high frequencies and that, when combined with a null allele, the RW mutation caused irregular stereocilia formation and decreased MYO15A at stereocilia tips. These findings support the ongoing research on the importance of MYO15A light chain binding on stereocilia formation and hearing impairments.
Krupp, Lilly, "The effect of the Arg1956Trp mutation in the IQ3 domain of MYO15A on stereocilia formation and hearing loss" (2022). Summer and Academic Year Student Reports. 2699.