| Project/Area Number |
17591164
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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 |
Dermatology
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| Research Institution | Gifu University |
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Principal Investigator |
ICHIKI Yoshiro Gifu University, Graduate School of Medicine, Associate professor, 大学院医学系研究科, 助教授 (30223093)
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| Co-Investigator(Kenkyū-buntansha) |
高木 肇 岐阜大学, 大学院・医学系研究科, 助教授 (70226752)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | keratin / epidermolysisbullosa |
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| Research Abstract |
We described two unrelated families in Japan and Korea having patients with an unique type of epidermolysis bullosa simplex named EBS with migratory circinate erythema and a novel mutation in the keratin gene, KRT5 ; i.e., frameshift and delayed stop codon inconsistent with any subtype described before. Electron microscopy of skin biopsies showed a reduction in the number of keratin intermediate filaments in the basal cells without tonofilament clumping. We identified a novel heterozygous deletion mutation (1649delG of KRT5) in both cases. This deletion is predicted to produce a mutant K5 protein with a frameshift of its terminal 41 amino acids, and 35 amino acids longer than the wild type K5 protein due to a delayed termination codon. Patient skin show positive reactivity to specific antibody which recognize the mutant elongated amino acids both in immunohistochemistry and immunoblotting.
Since the same abnormal elongated mutant KRT5 gene was found in the independent families, the predicted abnormal elongated keratin protein is likely to lead to an atypical clinical phenotype that has never been reported. Furthermore to investigate the function of elongated keratin 5 protein, keratin 5 expression in transgenic mice and transfected keratinocyte was analyzed. The transgenic mouse did not show any clinicopathological symptom on the skin, although immunoblotting showed the abnormal K5 protein in the epidermis. In the transfected keratinocyte analysis, the elongated K5 colocalized with normal endogeneous K14, suggested that mutant K5 does not disrupt keratin filament assembly.
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