2005 Fiscal Year Final Research Report Summary
Identification of a causative gene responsible for deafness, imbalance, and abnormal EEG in the WTC-dfk rat
| 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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| Keywords | Potassium channel / Long QT / deafness / achlorhydria / hypertension / disease model / rat / imbalance |
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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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[Journal Article] WTC deafness Kyoto (dfk) : a rat model for extensive investigations of Kcnq1 functions.2006
Author(s)
Gohma H, Kuramoto T, Kuwamura M, Okajima R, Tanimoto N, Yamasaki K, Nakanishi S, Kitada K, Makiyama T, Akao M, Kita T, Sasa M, Serikawa T
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Journal Title
Physiol Genomics 24(3)
Pages: 198-206
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The rat pink-eyed dilution (p) mutation : An identical intragenic deletion in pink-eye dilute-coat strains and several Wistar-derived albino strains2005
Author(s)
Kuramoto, T., Gohma, H., Kimura, K., Wedkind, D., Hedrich, HJ., Serikawa, T.
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Journal Title
Mammal Genome 16
Pages: 712-719
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mutation at the Lmx1a locus provokes aberrant brain development in the rat.2005
Author(s)
Kuwamura M, Muraguchi T, Matsui T, Ueno M, Takenaka S, Yamate J, Kotani T, Kuramoto T, Guenet JL, Kitada K, Serikawa T.
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Journal Title
Brain Res Dev Brain Res. 155(2)
Pages: 99-106
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Rat mutations cvd and hob with cerebellar malformations map to Chromosome 2.2004
Author(s)
Kuwamura, M., Ando, Y., Takada, A., Kanehara, T., Yamate, J., Kotani, T., Takashita, S., Kanbori, M., Kitada, K., Serikawa, T.
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Journal Title
Exp Anim 53(1)
Pages: 21-26
Description
「研究成果報告書概要(欧文)」より
