Downregulation of Dmxl2 disrupts the hearing development in mice.

Congenital hearing loss is a major type of sensorineural deafness. Recently, Dmxl2 has been identified as a new gene associated with familial deafness. However, its role in auditory development remains unclear. This study investigated the expression and localization of DmX-like protein 2 (DMXL2), encoded by Dmxl2, in the mouse cochlea at various postnatal stages. DMXL2 was predominantly expressed in inner and outer hair cells, with the highest levels at postnatal day 7, followed by a rapid decline, nearly disappearing by day 14. To elucidate Dmxl2's function, we administered short hairpin RNA (shRNA) targeting Dmxl2 to the cochlea within 24 h post-birth, effectively knocking down its expression in the mouse inner ear. This resulted in profound hearing loss in treated mice, accompanied by disruption of development of cochlear ribbon synapses and spiral ganglion cells (SGCs). In conclusion, our study demonstrates the critical role of Dmxl2 in hearing development, suggesting it as a potential molecular target for future gene therapy in hearing loss treatment.