Disruption of Hars2 in Cochlear Hair Cells Causes Progressive Mitochondrial Dysfunction and Hearing Loss in Mice

The study investigated the effects of disrupting the Hars2 gene in cochlear hair cells of mice, which is linked to Perrault syndrome 2 (PRLTS2) and hearing loss. Researchers found that knocking out Hars2 led to progressive hearing loss starting at postnatal day 30 (P30), with significant hair cell loss observed from P45. This was associated with increased reactive oxygen species (ROS) levels and activation of the mitochondrial apoptotic pathway. Despite normal synapse formation, there was reduced calcium influx and compromised synaptic exocytosis in inner hair cells, correlating with decreased auditory brainstem response amplitudes. Mitochondrial abnormalities, such as swelling and loss of cristae, were noted from P14, with outer hair cells experiencing more severe loss. The findings suggested that Hars2 knockout caused mitochondrial dysfunction and ROS stress, leading to hair cell synaptopathy and apoptosis, affecting inner and outer hair cells differently.