Chondrocyte‐specific Smad4 gene conditional knockout results in hearing loss and inner ear malformation in mice |
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| Authors: | Shi‐Ming Yang Zhao‐Hui Hou Guan Yang Ji‐Shuai Zhang Yin‐Yan Hu Jian‐He Sun Wei‐Wei Guo David z z He Dong‐Yi Han Wie‐Yen Young Xiao Yang |
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| Institution: | 1. Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China;2. Shi‐Ming Yang and Zhao‐Hui Hou contributed equally to this work.;3. Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, China;4. Hair Cell Biophysics Laboratory, Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska |
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| Abstract: | Smad4 is the central intracellular mediator of transforming growth factor‐β (TGF‐β) signaling, which plays crucial roles in tissue regeneration, cell differentiation, embryonic development, and regulation of the immune system. Conventional Smad4 gene knockout results in embryonic lethality, precluding its use in studies of the role of Smad4 in inner ear development. We used chondrocyte‐specific Smad4 knockout mice (Smad4Co/Co) to investigate the function of Smad4 in inner ear development. Smad4Co/Co mice were characterized by a smaller cochlear volume, bone malformation, and abnormalities of the osseous spiral lamina and basilar membrane. The development of the hair cells was also abnormal, as evidenced by the disorganized stereocilia and reduced density of the neuronal processes beneath the hair cells. Auditory function tests revealed the homozygous Smad4Co/Co mice suffered from severe sensorineural hearing loss. Our results suggest that Smad4 is required for inner ear development and normal auditory function in mammals. Developmental Dynamics, 2009. © 2009 Wiley‐Liss, Inc. |
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| Keywords: | BMPs signal Smad4 gene conditional knockout hearing loss inner ear development inner ear malformation |
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