Tprn is essential for the integrity of stereociliary rootlet in cochlear hair cells in mice
| Autor: | Xiaolong Fu, Haibo Wang, Xiujuan Li, Congzhe Hou, Tingting Zhang, Hailong Tu, Xiaoyang Sun, Yuqin Men, Aizhen Zhang, Yecheng Jin, Zhishuo Wang, Jiangang Gao, Jianfeng Li, Boqin Li, Sen Zhang, Yichen Zhou |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Hearing loss Stereocilia (inner ear) Hearing Loss Sensorineural Biology Deafness Stereocilia 03 medical and health sciences Mice 0302 clinical medicine Radixin Hair Cells Auditory otorhinolaryngologic diseases medicine Animals Inner ear Nonsyndromic deafness Outer hair cells Sequence Deletion Mice Knockout Membrane Proteins Proteins General Medicine medicine.disease Cell biology Cytoskeletal Proteins 030104 developmental biology medicine.anatomical_structure Mice Inbred CBA Microscopy Electron Scanning Female sense organs Hair cell medicine.symptom 030217 neurology & neurosurgery Central core disease |
| Zdroj: | Frontiers of medicine. 13(6) |
| ISSN: | 2095-0225 |
| Popis: | Tprn 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 of Tprn in hearing, we generated Tprn-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 of Tprn-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 in Tprn-null mice. The expression levels of radixin and β-actin significantly decreased.We propose that Tprn is critical to the retention of the integrity of the stereociliary rootlet. Loss of Tprn in Tprn-null mice caused the disruption of the stereociliary rootlet, which resulted in damage to stereociliary bundles and hearing impairments. The generated Tprn-null mice are ideal models of human hereditary deafness DFNB79. |
| Databáze: | OpenAIRE |
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