Objective To investigate the molecular mechanism of auditory pigmentary disorders using a KITF860S mutation hearing loss mouse model.Methods Long-term auditory electrophysiological tests were performed on individ-uals from a stable genetic KITF860S mouse model family with different phenotypes,together with histopathological obser-vations and whole genome transcriptional sequencing to analyze gene expression differences.Results Hearing pheno-types in heterozygous mice were not significantly different compared to wild-type mice initially,but showed progressive hearing loss at the age of 5 months;while homozygous mice demonstrated congenital moderate and severe hearing loss at an early age and total deafness at the age of 10 weeks.Transcriptional sequencing indicated down-regulated oxidative phosphorylation pathway in both homozygous and heterozygous KIT gene mutations as compared with wild-type mice,with variable up or down regulation of tight junction pathways.Conclusion Manifestations of auditory pigmentary dis-orders caused by KIT gene mutations are related to abnormal expression of target gene and proteins related to oxidative phosphorylation,tight junction and other pathways,resulting in abnormalities of basement membrane and vascular struc-tures,and ultimately hearing loss.Research on the molecular mechanism of KIT gene mutation is of great significance to enrich the human deafness gene pool,and provides a theoretical basis for gene therapy for related syndromes.
维普
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