title: Chondrocyte-specific Smad4 gene conditional knockout results in hearing loss and inner ear malformation in mice.
abstract: Smad4 is the central intracellular mediator of transforming growth factor-beta (TGF-beta) 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.
authors: Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. yangsm301@263.net
authors: Shi-ming
authors: SM
authors: Yang
authors: Zhao-hui
authors: ZH
authors: Hou
authors: Guan
authors: G
authors: Yang
authors: Ji-shuai
authors: JS
authors: Zhang
authors: Yin-yan
authors: YY
authors: Hu
authors: Jian-he
authors: JH
authors: Sun
authors: Wei-wei
authors: WW
authors: Guo
authors: David z z
authors: Dz
authors: He
authors: Dong-yi
authors: DY
authors: Han
authors: Wie-yen
authors: WY
authors: Young
authors: Xiao
authors: X
authors: Yang
mesh_terms: D000818:Animals; D001483:Base Sequence; D019902:Chondrocytes / Q000473:pathology / Q000502:physiology*; D003051:Cochlea / Q000002:abnormalities / Q000254:growth & development; D017931:DNA Primers / Q000235:genetics; D007758:Ear, Inner / Q000002:abnormalities* / Q000254:growth & development / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting / Q000379:methods; D006198:Hair Cells, Auditory / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009928:Organ Specificity; D010641:Phenotype; D051901:Smad4 Protein / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000473:pathology
chemical_list: D017931:DNA Primers; D051901:Smad4 Protein; C490810:Smad4 protein, mouse