| Project/Area Number |
11557122
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Tohoku University |
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Principal Investigator |
IKEDA Katsuhisa Tohoku University, Graduate school of Med., Associate Professor, 大学院・医学系研究科, 助教授 (70159614)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASE Tetsuaki Tohoku University, Hospital, Lecture, 医学部附属病院, 講師 (50169728)
OSHIMA Takeshi Tohoku University, Graduate school of Med., Research Associate, 大学院・医学系研究科, 助手 (40241608)
石谷 幸喜 グレラン製薬研究開発センター, 係長(研究職)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | Deafness gene / Mutation / Brn-4 / GJB2 / Konckout mice / Gen transfer / Endocochlear potential / K recysling / ブレイン-4 / 遺伝子移入 / 遺伝子 / 難聴 / Brn-4 / 内リンパ静止電位 / K^+イオン |
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| Research Abstract |
DFN3, an X-linked nonsyndromic mixed deafness is caused by mutations in BRN-4 gene, which encodes a POU transcription factor gene. By gene targeting technology 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 drastic reduction in endocochlear potential (EP). Electron microscopy revealed severe ultrastructural alterations in cochlear spiral ligament fibrocytes. Connexin 26 gene (GJB2) is known to be expressed in the cochlear fibrocytes and to play a important role in the auditory function. We have sequenced the GJB2 gene in 39 Japanese patients with prelingual sensorineural hearing loss. Three novel mutations were identified : a single nucleotide deletion (235delC), a 16 bp-deletion (176-191 del (16)) and a nonsense mutation (408c>a) in five unrelated patients. These findings indicate that GJB2 mutations are also responsible for prelingual deafness in Japan. These findings suggest that these fibrocytes, which are mesenchymal in origin and have been postulated to function in K^+ homeostasis, may play a critical role in auditory function and show a major cause of the hereditary deafness.
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