Smad5 haploinsufficiency leads to hair cell and hearing loss
Smad5 haploinsufficiency leads to hair cell and hearing loss
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DOI：
10.1002/dneu.20692
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发表时间：
2009-02
影响因子：
3
通讯作者：
Shi-ming Yang;Wei-Wei Guo-Wei;Yin-yan Hu;Yanxun Sun;Z. Hou;Jian-he Sun;Xiang Wang;D. He;S. Zhai;Wie-yen Young;Dong‐yi Han;Xiao Yang
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文献类型：
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作者：
Shi-ming Yang;Wei-Wei Guo-Wei;Yin-yan Hu;Yanxun Sun;Z. Hou;Jian-he Sun;Xiang Wang;D. He;S. Zhai;Wie-yen Young;Dong‐yi Han;Xiao Yang
Smads是一组相关的细胞内蛋白质，对将细胞表面的转化生长因子-β超家族的信号传递到细胞核至关重要。Smad5基因的敲除对胚胎是致命的。但单等位基因(±)的Smad5基因敲除仍可存活。我们使用Smad5杂合敲除(±)来确定Smad5在内耳形态和功能发育中的作用。原位杂交显示Smad5主要表达于毛细胞、螺旋神经节和支持细胞。使用听性脑干反应对听力阈值的测量表明，Smad5缺陷导致出生后4至24周内进行性听力损失。形态学检查显示，成年Smad5突变小鼠内耳出现细胞凋亡，外毛细胞明显丢失。我们的结果表明，Smad5介导的信号通路缺陷导致了毛细胞的凋亡，提示Smad5可能是一个与老年性耳聋有关的基因。©2008威利期刊公司开发神经生物学，2009
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