1999 Fiscal Year Final Research Report Summary
Genetics of Presbyacus's and its clinical application
| Project/Area Number |
10307039
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
TAKASAKA Tomonori Dept Otolaryngol, School of Medicine, Tohoku University, Professor, 大学院・医学系研究科, 教授 (80004646)
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| Co-Investigator(Kenkyū-buntansha) |
OSHIMA Takeshi Dept Otolaryngol, School of Medicine, Tohoku University, Instruct, 大学院・医学系研究科, 助手 (40241608)
KAWASE Tetsuaki Dept Otolaryngol, School of Medicine, Tohoku University, Assist Professor, 医学部・附属病院, 講師 (50169728)
IKEDA Katsuhisa Dept Otolaryngol, School of Medicine, Tohoku University, Assoc Professor, 大学院・医学系研究科, 助教授 (70159614)
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| Project Period (FY) |
1998 – 1999
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| Keywords | knockout mice / Brain-4 / Connexin-26 / Endocochlear potential / Hereditary deafness / Aging / DNA mutation |
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| Research Abstract |
DFN3, and 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 indicated 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ィイD1+ィエD1 homeostasis, may play a critical role in auditory function and show a major cause of the hereditary deafness.
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