Altered Cochlear Fibrocytes in a Mouse Model of DFN3 Nonsyndromic Deafness

• Published in: Science (American Association for the Advancement of Science) Vol. 285; no. 5432; pp. 1408 - 1411
• Main Authors: Minowa, O., Ikeda, K., Sugitani, Y., Oshima, T., Nakai, S., Katori, Y., Suzuki, M., Furukawa, M., Kawase, T., Zheng, Y., Ogura, M., Asada, Y., Watanabe, K., Yamanaka, H., Gotoh, S., Nishi-Takeshima, M., Sugimoto, T., Kikuchi, T., Takasaka, T., Noda, T.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 27-08-1999; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Auditory Tests; Biological and medical sciences; Cochlear Duct - metabolism; Cochlear Duct - pathology; Coding; Deafness; Deafness - genetics; Deafness - metabolism; Deafness - pathology; DNA-Binding Proteins; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Ear, Inner - metabolism; Ear, Inner - pathology; Ear, Middle - pathology; Ears & hearing; Endolymph - metabolism; Evoked Potentials, Auditory, Brain Stem; Female; Female animals; Females; Gene Expression; Gene Targeting; Genetic disorders; Genetic Linkage; Genetics; Hair cells; In Situ Hybridization; Individualized Instruction; Inner hair cells; Ion Transport; Laboratory animals; Male; Male animals; Males; Medical sciences; Membrane Potentials; Mice; Mice, Inbred C57BL; Mutagenesis; Mutation; Nerve Tissue Proteins; Non tumoral diseases; Otorhinolaryngology. Stomatology; Outer hair cells; Potassium - metabolism; POU Domain Factors; Spiral ganglion; Spiral ligament of cochlea; Stria vascularis; Transcription Factors - genetics; Transcription Factors - metabolism; X Chromosome; Animal model; Fibrocyte; Rodentia; Auditory disorder; Electrophysiology; Inner ear; Hearing loss; Vertebrata; Hearing; Mammalia; Mouse; Morphology; Cochlea; ENT disease; Genetics; Mutation; Transcription factor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.285.5432.1408

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.