2001 Fiscal Year Final Research Report Summary
Analysis of the pathogenesis of the hereditary non syndromic deafness caused by mutations in connection genes
| Project/Area Number |
12470358
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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 | Nagasaki University |
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Principal Investigator |
KIKUCHI Toshihiko Nagasaki University School of Medicine, Depart,ment of Otolaryngology, Assistant Professor, 医学部・附属病院, 講師 (70177799)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKASAKI Naoki Nagasaki University School of Medicine, Depart,ment of Otolaryngology, Instructor, 医学部・附属病院, 助手 (70274660)
KOBAYASHI Toshimitsu Nagasaki University School of Medicine, Depart,ment of Otolaryngology, Professor, 医学部, 教授 (80133958)
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| Project Period (FY) |
2000 – 2001
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| Keywords | nonsyndromic deafness / inner ear / gap junction / connexin / voltage-gated potassium channel / Kv3.1b / Kv3.4 / aquaporin |
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| Research Abstract |
1) Connexin 26 and connection 30 were expressed in both epithelial cell and connective tissue cell gap junction systems in the mammalian cochlea. In contrast, connection 31 was localized to the connective tissue cell gap junction system.
2) Voltage-gated potassium channel Kv3. 1 b-like immunoreactivity was present in the fibrocytes of the cochlear lateral wall. Immunostaining was also found in the interdental cells and the fibrocytes of the spiral limbus and in the supralimbal dark cells. Kv3.4-like immunoreactivity was present in the fibrocytes of the spiral ligament and the basal cells of the stria vascularis. In the organ of Corti, Kv3.4- like immunoreactivity was found in the hair cells and the neighboring supporting cells. The root cells and interdental cells were positively immunostained.
3) In the mammalian cochlea, aquaporin-1 and aquaporin-4 were found in some populations of the connective tissue cells and epithelial cells respectively.
4) The perilymphatlc per fusion with the long chain alcohol caused the depression of the endocochlear potential (FP). These findings suggested the functional significance of the gap junctional communication in the ion transporting mechanism in the mammalian cochlea.
5) In the mutant mouse lacking Brain-4, Na,K-ATPase-like immunoreactivity in the type II fibrocytes of the spiral ligament and the fibrocytes in the suprastrial zone was remarkably decreased. Connexin 26 was sparsely distributed among these fibrocytes in the cochlear lateral wall of this mutant mouse. These findings suggest that a dysfunction of fibrocytes and an interruption of the transcellular route via gap junctions can cause a depression of EP in the cochlea of this mutant mouse, and also suggest that the transcellular pathway via gap junctions plays a very important role in the transport of K+ ions in the cochlea.
6) Detailed physiological examinations were carried out in the cases of hereditary nonsyndromic deafness.
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