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Science 27 August 1999:
Vol. 285. no. 5432, pp. 1408 - 1411
DOI: 10.1126/science.285.5432.1408
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Reports

Altered Cochlear Fibrocytes in a Mouse Model of DFN3 Nonsyndromic Deafness

O. Minowa, 13* K. Ikeda, 2* Y. Sugitani, 13 T. Oshima, 2 S. Nakai, 13 Y. Katori, 2 M. Suzuki, 2 M. Furukawa, 2 T. Kawase, 2 Y. Zheng, 2 M. Ogura, 2 Y. Asada, 2 K. Watanabe, 2 H. Yamanaka, 13 S. Gotoh, 12 M. Nishi-Takeshima, 5 T. Sugimoto, 6 T. Kikuchi, 2 T. Takasaka, 2 T. Noda 134dagger

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.

1 Department of Cell Biology, The Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
2 Department of Otorhinolaryngology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
3 CREST, Japan Science and Technology Corporation, 4-1-8 Motomachi, Kawaguchi 332-0012, Japan.
4 Department of Molecular Genetics, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku Sendai 980-8575, Japan.
5 Department of Pharmacology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
6 Department of Anatomy, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi-shi, Osaka 570-8506, Japan.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: tnoda{at}ims.u-tokyo.ac.jp

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