The Studies Of Hearing Mechanism In Pou4f3 Mutant Mice

Object: An 8–base-pair deletion in the exon 2 of human Pou4f3 gene(c.884del8) was identified in Family H, which resulted in a truncated protein, impaired high-affinity binding in a dominant negative fashion, leading to inherited progressive hearing loss(DFNA15). However, it is still not clear about the physiological process and treatment methods. Thus, we used Pou4f3 muant mice as an animal model for DFNA15, and investigated the possible mechanism.Method: In this report, we generated heterozygous knockin mice by adding a mutant site containing an 8-bp deletion and a C-T interval in the end of exon 2 of Pou4f3 gene. The phenotype was assessed by hearing function(auditory brainstem response and distortion product otoacoustic emission), behavioral analysis vestibular function,inner ear morphology. Constructed the p GL3 Basic-Espin/Myo6 promoter expression vector, transfected into HEK293 T cells to observe Pou4f3 on Espin and Myo6 of gene expression and regulation using dual luciferase reporter assay system in vitro.Result: The mutant mice displayed an elevation of auditory brianstem response(ABR) thresholds responsing to click and tones of different frequencies, especially high frequency, in the similar pattern of human’s clinic phenotype. DPOAE can derivate in mutant and control mice. The mutant mice show poor vestibular function. Transmission electron microscopy the ultrastructure of the cochlear hair cells to display mutant mice inner hair cells mitochondrial edema, cavitation phenomenon. We successfully constructed a p GL3 Basic-Espin/Myo6 promoter expression vector.Transcription factor Pou4f3 mutant can affect Espin and Myo6 gene expression.Conclusion: Pou4f3 gene mutation impact inner hair cells structure and function of the mitochondria, thereby affecting the inner hair cells perception of sound. One of the pathogenesis of DFNA15 deafness, may be due to the Pou4f3 mutations of the transcription factor, to produce a truncated mutants having a dominant negative effect, affect the hair cell cilia polar growth, the ciliated fusion and the phenomenon of giant cilia, resulting abnormal external signal electromechanical conversion process, and ultimately lead to a decline in auditory function.