| Project/Area Number |
14571608
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Tokyo Medical and Dental University Hospital |
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Principal Investigator |
UZAWA Masamichi (2003-2004) Tokyo Medical and Dental University Hospital, Department of Otolaryngology, MD, Reader, 医学部附属病院, 助手 (10361700)
岡村 洋沖 (2002) 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (50244372)
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| Co-Investigator(Kenkyū-buntansha) |
KITAMURA Ken Graduate School of Tokyo Medical and Dental University, Department of Otolaryngology, MD, Ph.D., Chairman and Professor, 大学院・医歯学総合研究科, 教授 (90010470)
OKAMURA Hiro-oki Tokyo Medical and Dental University Hospital, Department of Otolaryngology, MD, Ph.D., Assistant Professor, 医学部附属病院, 講師 (50244372)
SUMI Takuro Tokyo Medical and Dental University Hospital, Department of Otolaryngology, MD, Reader, 医学部附属病院, 助手 (20361701)
野口 佳裕 東京医科歯科大学, 大学院・医歯学総合研究科, 講師 (50282752)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Mice / Deafness / Endolymph / CLC-KB / NKCC / Homeobox / Six 1 / Otic Gene / II型糖尿病 / DPOAE / 静止電位 / 血管条 / ラセン神経節 / Lepr ob / ob / Lepr db / db / mice / C57BL / 6 / CLC-KB / cochlea / EGFP / Stria / Spiral ligament / NKCC / イオン輸送 / 細胞生物学 / 増感方法論 / Na-K-Cl cotransporter / Furosemide / Cl^-チャンネル / トランスジェニックマウス |
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| Research Abstract |
CLC-KB was seen not only on the stria vascularis but on spiral ligament and limbal fibrocytes, interdental cells and satellite cells of spiral ganglion neurons that are known to possess both Na, K-ATPase and the Na-K-Cl co-transporter (NKCC). These results suggest that some fibrocytes possessing both the CLC-KB and the NKCC may be involved in the regulation of cell volume, transport and recycling of Cl- such as is seen in the stria vascularis. Moreover, these fibrocytes may recycle Cl- through CLC that accompany Na+ and K+ into the cell via NKCC. We also investigate Six1 mutation mice. Six1 is a member of the Six family homeobox genes, which function as components of the Pax-Six-Eya-Dach gene network to control organ development. Six1 is expressed in otic vesicles, nasal epithelia, branchial arches/pouches, nephrogenic cords, somites and a limited set of ganglia. In this study, we established Six1-deficient mice and found that development of the inner ear, nose, thymus, kidney and skeletal muscle was severely affected. Six1-deficient embryos were devoid of inner ear structures, including cochlea and vestibule, while their endolymphatic sac was enlarged. The inner ear anomaly began at around E1O.5 and Six1 was expressed in the ventral region of the otic vesicle in the wild-type embryos at this stage. In the otic vesicle of Six 1-deficient embryos, expressions of Otx1, Otx2, Lfng and Fgf3, which were expressed ventrally in the wild-type otic vesicles, were abolished, while the expression domains of Dlx5, Hmx3, Dach1 and Dach2, which were expressed dorsally in the wild-type otic vesicles, expanded ventrally. Our results indicate that Six1 functions as a key regulator of otic vesicle patterning at early embryogenesis and controls the expression domains of downstream otic genes responsible for respective inner ear structures.
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