한빛사논문
- 조회2,985
Woongsu Hana,b,1, Jeong-Oh Shinc,1, Ji-Hyun Mac,1, Hyehyun Minc,d, Jinsei Jungb,e, Jinu Leef, Un-Kyung Kimg, Jae Young Choib,e, Seok Jun Moonh, Dae Won Mooni,2, Jinwoong Bokb,c,d,e,2, and Chul Hoon Kima,b,d,2
aDepartment of Pharmacology, Yonsei University College of Medicine, 03722 Seoul, Korea; bBrain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 03722 Seoul, Korea cDepartment of Anatomy, Yonsei University College of Medicine, 03722 Seoul, Korea; dSeverance Biomedical Science Institute, Yonsei University College of Medicine, 03722 Seoul, Korea; eDepartment of Otorhinolaryngology, Yonsei University College of Medicine, 03722 Seoul, Korea; fYonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 21983 Inchon, Korea; gDepartment of Biology, Kyungpook National University, 41566 Daegu, Korea; hDepartment of Oral Biology, Yonsei University College of Dentistry, 03722 Seoul, Korea; and iDepartment of New Biology, Daegu Gyeongbuk Institute of Science and Technology, 42988 Daegu, Korea
1W.H., J.-O.S., and J.-H.M. contributed equally to this work.
2To whom correspondence may be addressed.
Abstract
Outer hair cells (OHCs) play an essential role in hearing by acting as a nonlinear amplifier which helps the cochlea detect sounds with high sensitivity and accuracy. This nonlinear sound processing generates distortion products, which can be measured as distortion-product otoacoustic emissions (DPOAEs). The OHC stereocilia that respond to sound vibrations are connected by three kinds of extracellular links: tip links that connect the taller stereocilia to shorter ones and convey force to the mechanoelectrical transduction channels, tectorial membrane-attachment crowns (TM-ACs) that connect the tallest stereocilia to one another and to the overlying TM, and horizontal top connectors (HTCs) that link adjacent stereocilia. While the tip links have been extensively studied, the roles that the other two types of links play in hearing are much less clear, largely because of a lack of suitable animal models. Here, while analyzing genetic combinations of tubby mice, we encountered models missing both HTCs and TM-ACs or HTCs alone. We found that the tubby mutation causes loss of both HTCs and TM-ACs due to a mislocalization of stereocilin, which results in OHC dysfunction leading to severe hearing loss. Intriguingly, the addition of the modifier allele modifier of tubby hearing 1 in tubby mice selectively rescues the TM-ACs but not the HTCs. Hearing is significantly rescued in these mice with robust DPOAE production, indicating an essential role of the TM-ACs but not the HTCs in normal OHC function. In contrast, the HTCs are required for the resistance of hearing to damage caused by noise stress.
hearing loss, outer hair cell, stereocilia, tubby, stereocilin
논문정보
- Research article
- 2020년 05월 (BRIC 등록일 2020-05-07)
- 국내 연구진
- 의약학 > 신경의학
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