Tprn is essential for the integrity of stereociliary rootlet in cochlear hair cells in mice

AbstractTprn encodes the taperin protein, which is concentrated in the tapered region of hair cell stereocilia in the inner ear. In humans,TPRN mutations cause autosomal recessive nonsyndromic deafness (DFNB79) by an unknown mechanism. To determine the role ofTprn in hearing, we generatedTprn-null mice by clustered regularly interspaced short palindromic repeat/Cas9 genome-editing technology from a CBA/CaJ background. We observed significant hearing loss and progressive degeneration of stereocilia in the outer hair cells ofTprn-null mice starting from postnatal day 30. Transmission electron microscopy images of stereociliary bundles in the mutant mice showed some stereociliary rootlets with curved shafts. The central cores of the stereociliary rootlets possessed hollow structures with surrounding loose peripheral dense rings. Radixin, a protein expressed at stereocilia tapering, was abnormally dispersed along the stereocilia shafts inTprn-null mice. The expression levels of radixin and β-actin significantly decreased.We propose thatTprn is critical to the retention of the integrity of the stereociliary rootlet. Loss ofTprn inTprn-null mice caused the disruption of the stereociliary rootlet, which resulted in damage to stereociliary bundles and hearing impairments. The generatedTprn-null mice are ideal models of human hereditary deafness DFNB79.
Source: Frontiers of Medicine - Category: General Medicine Source Type: research