Loss of Myh14 Increases Susceptibility to Noise-Induced Hearing Loss in CBA/CaJ Mice

Abstract

MYH14 is a member of the myosin family, which has been implicated in many motile processes such as ion-channel gating, organelle translocation, and the cytoskeleton rearrangement. Mutations in MYH14 lead to a DFNA4-type hearing impairment. Further evidence also shows that MYH14 is a candidate noise-induced hearing loss (NIHL) susceptible gene. However, the specific roles of MYH14 in auditory function and NIHL are not fully understood. In the present study, we used CRISPR/Cas9 technology to establish a Myh14 knockout mice line in CBA/CaJ background (now referred to as Myh14−/− mice) and clarify the role of MYH14 in the cochlea and NIHL. We found that Myh14−/− mice did not exhibit significant hearing loss until five months of age. In addition, Myh14−/− mice were more vulnerable to high intensity noise compared to control mice. More significant outer hair cell loss was observed in Myh14−/− mice than in wild type controls after acoustic trauma. Our findings suggest that Myh14 may play a beneficial role in the protection of the cochlea after acoustic overstimulation in CBA/CaJ mice.

Mechanistic insights into the active site and allosteric communication pathways in human nonmuscle myosin-2C

“…Disruption of the pathway by mutation of R788 to a glutamate causes the loss of its enzymatic signatures and results in a high duty ratio motor. Importantly, several key residues involved in the allosteric communication pathway are implicated in the onset and progression of debilitating human diseases ( Fu et al, 2016 ; Donaudy et al, 2004 ; Kim et al, 2017 ). Missense mutation G376C is in proximity to residues C324 of helix J and R328 of the JK-loop ( Figure 4—figure supplement 1F ).…”

Tuberous sclerosis complex–mediated mTORC1 overactivation promotes age-related hearing loss

“…Auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) were measured as described previously (ref. 62; and see Supplemental Methods).…”

Non-muscle myosin-2 contractility-dependent actin turnover limits the length of epithelial microvilli

“…NM2C exhibits specific expression to pituitary gland and glial cells, as well as inner ear sensory, intestinal, and kidney epithelia (32). Mutations in MYH14 have been linked to hearing loss, peripheral neuropathies, and developmental defects in the lower gastrointestinal tract (33)(34)(35)(36)(37)(38)(39)(40)(41). The parallel perturbation of both inner ear and intestinal epithelial systems by mutations in MYH14 is intriguing, as actin bundled-supported stereocilia found on the apical surface of hair cells are closely related to microvilli found on solute transporting epithelia, and may share mechanisms of assembly and maintenance (42,43).…”