The microRNA-183/96/182 Cluster is Essential for Stereociliary Bundle Formation and Function of Cochlear Sensory Hair Cells
| Autor: | Jinsheng Zhang, Chithra Muraleedharan, David N. Furness, Ruishuang Geng, Shunbin Xu, Vincent Lin, Alain Dabdoub |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Hearing loss Mutant Morphogenesis lcsh:Medicine Biology Article Stereocilia 03 medical and health sciences Mice 0302 clinical medicine SOX2 CLIC5 Hair Cells Auditory medicine otorhinolaryngologic diseases Animals Inner ear lcsh:Science Cochlea Cells Cultured QM Mice Knockout Multidisciplinary Hair Cells Auditory Inner lcsh:R QP Cell biology Mice Inbred C57BL MicroRNAs 030104 developmental biology medicine.anatomical_structure Animals Newborn Organ of Corti Multigene Family biology.protein lcsh:Q sense organs medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) |
| ISSN: | 2045-2322 |
| Popis: | The microRNA (miR)-183/96/182 cluster plays important roles in the development and functions of sensory organs, including the inner ear. Point-mutations in the seed sequence of miR-96 result in non-syndromic hearing loss in both mice and humans. However, the lack of a functionally null mutant has hampered the evaluation of the cluster’s physiological functions. Here we have characterized a loss-of-function mutant mouse model (miR-183CGT/GT), in which the miR-183/96/182 cluster gene is inactivated by a gene-trap (GT) construct. The homozygous mutant mice show profound congenital hearing loss with severe defects in cochlear hair cell (HC) maturation, alignment, hair bundle formation and the checkboard-like pattern of the cochlear sensory epithelia. The stereociliary bundles retain an immature appearance throughout the cochlea at postnatal day (P) 3 and degenerate soon after. The organ of Corti of mutant newborn mice has no functional mechanoelectrical transduction. Several predicted target genes of the miR-183/96/182 cluster that are known to play important roles in HC development and function, including Clic5, Rdx, Ezr, Rac1, Myo1c, Pvrl3 and Sox2, are upregulated in the cochlea. These results suggest that the miR-183/96/182 cluster is essential for stereociliary bundle formation, morphogenesis and function of the cochlear HCs. |
| Databáze: | OpenAIRE |
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