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Updated: May 29, 2025

Dissection of the Auditory Bulla in Postnatal Mice: Isolation of the Middle Ear Bones and Histological Analysis
Published on: January 4, 2017
Biallelic variants of SEMA3F are associated with nonsyndromic hearing loss
Sun Young Joo1, Hyehyun Min2, Jung Ah Kim1
1Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Won Sang Institute for Hearing Loss, Seoul 03722, Republic of Korea.
Abstract:
It is crucial to manage hearing loss and its associated public health impacts. In this study, we aimed to understand the role of Sema3f in the development and maintenance of the auditory system. Inner ear-specific Sema3f knockout mice exhibited hearing loss at 8 weeks with an elevated threshold for auditory brainstem response and an absent threshold for distortion product optoacoustic emission tests. Additionally, an increased number of outer hair cells and abnormal patterns of spiral ganglion neuron projections in the outer hair cell regions were observed. Through the analyses of sequencing data from 558 families with hearing loss, we identified biallelic variants of SEMA3F, which encodes semaphorin-3F, in one of the families. In the family, the proband showed profound progressive nonsyndromic hearing loss with congenital onset. In vitro analysis revealed that the identified missense variants decreased the furin-mediated processing of SEMA3F and abolished the cellular abilities of SEMA3F, which collapsed the filamentous actin cytoskeleton in human umbilical vein-derived endothelial cells. Our data suggest that SEMA3F is essential for normal hearing and is associated with nonsyndromic hearing loss in humans.
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