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Smad5 haploinsufficiency leads to hair cell and hearing loss
Author(s) -
Yang ShiMing,
Guo WeiWei,
Hu YinYan,
Sun YanXun,
Hou ZhaoHui,
Sun JianHe,
Wang Xiang,
He David Z.Z.,
Zhai SuoQiang,
Young WieYen,
Han DongYi,
Yang Xiao
Publication year - 2008
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.20692
Subject(s) - haploinsufficiency , spiral ganglion , presbycusis , hair cell , inner ear , hearing loss , biology , stereocilia (inner ear) , microbiology and biotechnology , anatomy , genetics , phenotype , audiology , medicine , gene
The Smads are a group of related intracellular proteins critical for transmitting the signals to the nucleus from the transforming growth factor‐β superfamily at the cell surface. Knockout of the Smad5 is embryonic lethal. However, the Smad5 knockout of single allele (±) could survive. We used Smad5 heterozygous knockout (±) to determine the role of Smad5 in the development of inner ear morphology and function. In situ hybridization showed that Smad5 was expressed predominantly in hair cells, spiral ganglion, and supporting cells. Measurements of hearing thresholds using auditory brainstem response showed that Smad5 defect resulted in progressive hearing loss between 4 and 24 weeks after birth. Morphological examination revealed apoptosis in the inner ear, with significant loss of outer hair cells in adult Smad5 mutant mice. Our results indicated that deficiency in the Smad5‐mediated signaling resulted in apoptosis of hair cells, suggesting Smad5 is a gene that may be related with presbycusis. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2009