Methionine Sulfoxide Reductase A Knockout Mice Show Progressive Hearing Loss and Sensitivity to Acoustic Trauma

Methionine sulfoxide reductases (MsrA andMsrB) protect the biological activity of proteins from oxidative modifications to methionine residues and are important for protecting against the pathological effects of neurodegenerative diseases. In the current study, we characterized the auditory phenotype of theMsrA knockout mouse. YoungMsrA knockout mice showed small high-frequency threshold elevations for auditory brainstem response and distortion product otoacoustic emission compared to those of wild-type mice, which progressively worsened in olderMsrA knockout mice.MsrA knockout mice showed an increased sensitivity to noise at young and older ages, suggesting thatMsrA is part of a mechanism that protects the cochlea from acoustic damage.MsrA mRNA in the cochlea was increased following acoustic stimulation. Finally, expression of mRNAMsrB1 was compromised at 6 months old, but not in youngerMsrA knockout mice (compared to controls). The identification ofMsrA in the cochlea as a protective mediator from both early onset hearing loss and acoustic trauma expands our understanding of the pathways that may induce protection from acoustic trauma and foster further studies on how to prevent the damaging effect of noise exposure through Msr-based therapy.Audiol Neurotol 2018;23:20 –31

Source: Audiology and Neurotology - June 21, 2018 Category: Audiology Source Type: research