Functional Study Of MTOR In Mice Auditory System

mTOR is a mammalian target of rapamycin,a serine/threonine protein kinase in the PI3K-related kinase(PIKK)family.It is a protein kinase that regulates the initial stage of protein translation.mTOR is extremely conserved in mammals and is expressed in almost all cell types,and its encoded protein size is 289KD.mTOR exists in cells in two different complexes,mTORCl and mTORC2.mTORC1 drives a variety of anabolic pathways,including protein synthesis,ribosome production,lipogenesis and nucleotide synthesis,all of which are important for cell and tissue growth.mTORC2 plays an important role in the actin cytoskeleton,cell survival and so on.Studies have shown that mTOR signaling pathway can lead to many major diseases,such as epilepsy,diabetes,tuberous sclerosis syndrome and tumors.However,the role of mTOR in the auditory system is currently unclear.The purpose of this study is to study the role of mTOR in the auditory system and to provide an animal model for auditory development-related diseases to provide scientific evidence for its prevention and treatmentUsing the Cre-LoxP conditional knockout technique,the Atoh1-mTOR knockout mouse model was established in this study.By studying the phenotypic changes in mTOR knockout mice,we explored the function of mTOR in the auditory system Cochlear sections immunofluorescence staining was used to determine the localization of mTOR in the epithelial cells of the cochlea.The results showed that mTOR was localized in the nucleus of hair cells,and the expression of inner hair cells was higher than that of outer hair cells.In this study,the auditory brainstem response(ABR)was used to detect hearing changes in mice and it was found that mTOR knockout mice had no significant change in auditory threshold compared to wild-type mice within 30 days after birth(P30).Serious hearing loss occurs around 45 days after birth(P45).There was no significant difference in outer hair cells by DPOAE assay.H&E staining of cochlea paraffin sections was used to observe the morphological changes of the cochlea.It was found that there was no abnormality in the cochlea morphology of mTOR knockout mice.Immunofluorescence staining by basement membrane immunofluorescence revealed that there was no significant change in the morphology and number of hair cells in mTOR knockout mice compared with wild-type mice around 45 days,but the number of synapses in mTOR knockout mice was significantly decreased.According to the analysis,there are statistical differences.This topic successfully established the mTOR conditional knockout mouse model.This model can be used as an ideal animal model to study the function of mTOR in the inner auditory system.The results showed that mTOR knockout mice had a normal hearing threshold 30 days after birth,but severe hearing loss occurred in mice 45 days after birth and the number of synapses was significantly reduced.These results demonstrate that mTOR affects the auditory function of mice by affecting synaptic changes.