Elmod3 knockout leads to progressive hearing loss and abnormalities in cochlear hair cell stereocilia
| Autor: | Jing Liu, Denise Yan, Xianlin Liu, Sida Huang, Yong Feng, Jie Sun, Anhai Chen, Yalan Liu, Wu Li, Jiangang Gao, Jie Ling, Lingyun Mei, Taoxi Li, Xuezhong Liu |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Hearing loss Stereocilia (inner ear) Deafness Biology Stereocilia Mice 03 medical and health sciences 0302 clinical medicine GTP-Binding Proteins otorhinolaryngologic diseases Genetics medicine Animals Hearing Loss Molecular Biology Cytoskeleton Genetics (clinical) Cochlea 030304 developmental biology Mice Knockout Vestibular system 0303 health sciences Stereocilium Hair Cells Auditory Inner GTPase-Activating Proteins General Medicine Actin cytoskeleton Actins Cell biology Mice Inbred C57BL Actin Cytoskeleton Hair Cells Auditory Outer medicine.anatomical_structure Organ of Corti Mutation Knockout mouse Female General Article sense organs medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Hum Mol Genet |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | ELMOD3, an ARL2 GTPase-activating protein, is implicated in causing hearing impairment in humans. However, the specific role of ELMOD3 in auditory function is still far from being elucidated. In the present study, we used the CRISPR/Cas9 technology to establish an Elmod3 knockout mice line in the C57BL/6 background (hereinafter referred to as Elmod3−/− mice) and investigated the role of Elmod3 in the cochlea and auditory function. Elmod3−/− mice started to exhibit hearing loss from 2 months of age, and the deafness progressed with aging, while the vestibular function of Elmod3−/− mice was normal. We also observed that Elmod3−/− mice showed thinning and receding hair cells in the organ of Corti and much lower expression of F-actin cytoskeleton in the cochlea compared with wild-type mice. The deafness associated with the mutation may be caused by cochlear hair cells dysfunction, which manifests with shortening and fusion of inner hair cells stereocilia and progressive degeneration of outer hair cells stereocilia. Our finding associates Elmod3 deficiencies with stereocilia dysmorphologies and reveals that they might play roles in the actin cytoskeleton dynamics in cochlear hair cells, and thus relate to hearing impairment. |
| Databáze: | OpenAIRE |
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