Smad5 haploinsufficiency leads to hair cell and hearing loss.
The Smads are a group of related intracellular proteins critical for transmitting the signals to the nucleus from the transforming growth factor-beta 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.
Yang
Shi-Ming
SM
Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, People's Republic of China. yangsm301@263.net
Guo
Wei-Wei
WW
Hu
Yin-Yan
YY
Sun
Yan-Xun
YX
Hou
Zhao-Hui
ZH
Sun
Jian-He
JH
Wang
Xiang
X
He
David Z Z
DZ
Zhai
Suo-Qiang
SQ
Young
Wie-Yen
WY
Han
Dong-Yi
DY
Yang
Xiao
X
D000161:Acoustic Stimulation / Q000379:methods; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics*; D001309:Auditory Threshold / Q000502:physiology; D003051:Cochlea / Q000254:growth & development / Q000473:pathology* / Q000648:ultrastructure; D006198:Hair Cells, Auditory / Q000473:pathology* / Q000648:ultrastructure; D034381:Hearing Loss / Q000235:genetics*; D020287:In Situ Nick-End Labeling / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron / Q000379:methods; D051902:Smad5 Protein / Q000172:deficiency* / Q000378:metabolism*
D051902:Smad5 Protein; C497798:Smad5 protein, mouse