| Project/Area Number |
14370537
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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 | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | JUNTENDO UNIVERSITY (2003)
Tohoku University (2002) |
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Principal Investigator |
IKEDA Katsuhisa JUNTENDO UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (70159614)
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| Co-Investigator(Kenkyū-buntansha) |
ENOMOTO Fuyuki JUNTENDO UNIVERSITY, SCHOOL OF MEDICINE, SENIOR LECTURER, 医学部, 講師 (00281361)
MATSUBARA Yoichi TOHOKU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (00209602)
MINOWA Osamu RIKEN INSTITUTE, GENOME SCIENCE GENERAL CENTER, SENIOR RESEARCHER, ゲノム科学総合研究センター, 主任研究員 (00181967)
鈴木 雅明 東北大学, 医学部附属病院, 助手 (40261630)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2003: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Random mutagenesis / Congenital deafness / Auditory brainstem response / Animal model / Organ of Corti / EUN / 難聴遺伝子 / ランダムミュータジェネーシス / 蝸牛 / 有毛細胞 / 血管条 / ラセン神経節 |
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| Research Abstract |
In recent 5 years, twenty novel genes responsible for hereditary deafness have been discovered in foreign countries, but no new identification of deafness gene has never appeared in Japan. It will be explained by small size of Japanese families, difficulty in classification of phenotype of deafness, difficulty in standard genetic approach to identify novel genes such as positioning cloning and candidate gene approach. Therefore, we use random mutagenesis project, which includes mutagenesis of genes in mouse and screening of deafness, and identification of the responsible gene in order to discover novel deafness genes. Auditory analysis of the mouse model for deafness provides the underlying mechanism of deafness. Furthermore, this animal research can be applied to human study, leading to possibilities of clinical application.
We created point mutation of deafness gene in embryonic stem cell by EUN and screened the mice created by auditory brainstem response. Totally 56 mice of 13 lines could be detected deafness. The detailed analysis of auditory responses by tone burst resulted in 12 animals of slight hearing loss, 22 animals of moderate hearing loss, and 32 animals of severe hearing loss. Based upon histopathological analysis, pathological findings were observed in 13 animal in the organ of Corti, 9 in spiral ganglion cells, 5 in stria vascularis, 4 spiral ligament and 2 in tectorial membrane, and no abnormal finding was observed in 2 animals. We discovered that the gene encoding Ca-ATPase was responsible for de at least one line of these mouse models.
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