Altered cochlear fibrocytes in a mouse model of DFN3 nonsyndromic deafness.
DFN3, an X chromosome-linked nonsyndromic mixed deafness, is caused by mutations in the BRN-4 gene, which encodes a POU transcription factor. Brn-4-deficient mice were created and found to exhibit profound deafness. No gross morphological changes were observed in the conductive ossicles or cochlea, although there was a dramatic reduction in endocochlear potential. Electron microscopy revealed severe ultrastructural alterations in cochlear spiral ligament fibrocytes. The findings suggest that these fibrocytes, which are mesenchymal in origin and for which a role in potassium ion homeostasis has been postulated, may play a critical role in auditory function.
Minowa
O
O
Department of Cell Biology, The Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
Ikeda
K
K
Sugitani
Y
Y
Oshima
T
T
Nakai
S
S
Katori
Y
Y
Suzuki
M
M
Furukawa
M
M
Kawase
T
T
Zheng
Y
Y
Ogura
M
M
Asada
Y
Y
Watanabe
K
K
Yamanaka
H
H
Gotoh
S
S
Nishi-Takeshima
M
M
Sugimoto
T
T
Kikuchi
T
T
Takasaka
T
T
Noda
T
T
D000818:Animals; D003053:Cochlear Duct / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins; D003638:Deafness / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007758:Ear, Inner / Q000378:metabolism / Q000473:pathology; D004432:Ear, Middle / Q000473:pathology; D004710:Endolymph / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting; D008040:Genetic Linkage; D017403:In Situ Hybridization; D017136:Ion Transport; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; D011188:Potassium / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014960:X Chromosome
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; D014157:Transcription Factors; C074067:Pou3f4 protein, mouse; D011188:Potassium