Effect And Mechanism Of Rimbp2 Gene On Cochlear Hair Cells In Mice

Hearing loss is one of the most common sensory disorders,which has become a global socio-political and economic health problem.According to the latest data from the World Health Organization（WHO）,as of 2018,466 million people worldwide were suffering from hearing impairment,and the number is still growing.Genetic factors are the main causes of sensorineural deafness.The discovery and study of deafness genes are of great significance in clinical practice.RIMBP2（Rab3-interacting molecule binding protein 2,RIMBP2）is a member of the synaptic activity domain protein binding protein family.It has been reported that RIMBP2 can affect the precise localization of presynaptic proteins and then regulate signal transmission in central neurons and hippocampal neurons by interacting with Rab3-interacting molecule（RIM）and other presynaptic-related proteins.However,the effect of RIMBP2 in the mouse inner ear still remains unclear.In this study,we used the Rimbp2 knockout mouse to further explore the role of Rimbp2 in mouse hearing and the molecular mechanism.We have demonstrated that Rimbp2 was expressed in the cytoplasm of mouse inner ear hair cells.Auditory brainstem response（ABR）tests showed that the hearing threshold of Rimbp2 knockout mice was significantly increased from P21（postnatal day 21）,and the latency of ABRⅠwave was prolonged and the amplitude was significantly decreased.These results indicated that Rimbp2 plays an irreplaceable role in the hearing of mice.From P21 to P60,the cilium of mouse cochlear hair cells did not change in morphology or polarity due to Rimbp2 knockout.However,the outer hair cells underwent apoptosis.Through whole-cell patch-clamp electrophysiological recording of mouse cochlear hair cells and spiral ganglion neurons,we also found that the exocytosis of the cochlear hair cells was severely impaired in Rimbp2^-/-mice,the postsynaptic electrical response and miniature excitatory postsynaptic current（m EPSC）of SGNs had a significant reduction,but the development of spiral ganglion neurons in knockout mice was normal.This suggested that the abnormal connections between hair cells and spiral ganglion neurons may be responsible for the auditory dysfunction of Rimbp2 knockout mice.There was no significant difference in the number of synapses compared with the wild-type mice,but the synapses appeared significantly closer to the nucleus in the Rimbp2 knockout mice.In conclusion,our study showed that Rimbp2 played an important role in the electrochemical transmission of mice auditory signals.This study will provide new ideas and research basis for further research on the molecular mechanism of Rimbp2regulation in hearing,so as to enrich the research on deafness genes and provide a theoretical basis for clinical prevention,diagnosis,and treatment of deafness.