| Project/Area Number |
15300141
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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 |
Laboratory animal science
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| Research Institution | Kyoto University |
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Principal Investigator |
KURAMOTO Takashi Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (20311409)
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| Co-Investigator(Kenkyū-buntansha) |
KUWAMURA Mitsuru Osaka Prefecture University, Veterinary Pathology, Lecturer, 生命環境科学研究科, 講師 (20244668)
AKAIKE Akinori Kyoto University, Graduate School of Pharmacology, 薬学研究科, 教授 (80135558)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥16,800,000 (Direct Cost: ¥16,800,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | Potassium channel / Long QT / deafness / achlorhydria / hypertension / disease model / rat / imbalance / ボジショナルクローニング / コアイソジェニック / 低体重 / 行動異常 / ポジショナルクローニング / 突然変異 / 常染色体劣勢遺伝 / 連鎖解析 / 遺伝子マッピング |
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| Research Abstract |
KCNQ1 forms K^+ channels by assembly with regulatory subunit KCNE proteins and plays a key role in the K^+ homeostasis in a variety of tissues. In the heart, KCNQ1 is co-assembled with the KCNE1 to produce a cardiac-delayed rectifier K^+ current. In the inner ear, KCNQ1/KNCE1 complex maintains the high concentration of K^+ in the endolymph. In the stomach, KCNQ1 is co-assembled with KCNE2 to form the K^+ exflux channel that is essential for gastric acid secretion. In the colon and small intestine, KCNQ1 is co-assembled with KCNE3 to play an important role in transepithelial cAMP-stimulated Cl^- secretion. For further understanding of Kcnq1 function in vivo, an animal model has been required. Here we reported the identification of a coisogenic Kcnq1 mutant rat, named deafness Kyoto (dfk), and the characterization of its phenotypes. WTC-dfk rats carried intragenic deletion at the Kcnq1 gene, and showed impaired gain of weight, deafness and imbalance resulting from the marked reduction of endolymph, prolonged QT interval in the ECG, and gastric achlorhydria associated with hypertrophic gastric mucosa. Surprisingly, WTC-dfk rats showed hypertension, which suggested that Kcnq1 might be involved in the regulation of blood pressure. These findings suggest that WTC-dfk rats could represent a powerful tool for studying the physiological functions of KCNQ1 and for the establishment of new therapeutic procedures for Kcnq1-related diseases.
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