| Project/Area Number |
20K08666
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Akita University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Dowling-Degos disease / 遺伝性色素異常症 / 常染色体優性遺伝形式 / Dowling-Degos病 / モデルマウス / POFUT1 / 網状肢端色素沈着症 / ADAM10 |
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| Outline of Research at the Start |
Dowling-Degos病(DDD)は網状の色素斑が思春期以降に出現する常染色体優性遺伝形式の遺伝性色素異常症である。POFUT1、POGLUT1が原因遺伝子として同定されたが、どのようにして特徴的に皮疹が生じるのかという病態は未だ明らかになっていない。本研究では、DDDモデルマウスを確立させ、① DDD発症に関与する糖鎖修飾の基質タンパクを検討して病態解明、さらに、② 治療法開発を行う。
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| Outline of Final Research Achievements |
Dowling-Degos disease (DDD) shows an autosomal dominant inheritance pattern, with slightly depressed reticulate pigmented patches appearing in the axilla, elbow, neck, and other intertriginous areas. In 2006, KRT5 was identified as the causative gene, followed by POFUT1, POGLUT1, and PSENEN in 2013. POFUT1 and POGLUT1 are involved in protein glycosylation, while PSENEN constitutes γ-secretase. In the present study, we tried to identify which substrate proteins in which skin cells are glycosylated by POFUT1, but no significant results were obtained. Regarding the development of therapeutic agents, we developed a rapid screening system and it wasused to screen the drug library to identify new candidate drugs. Unfortunately, no candidate drug was obtained.
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| Academic Significance and Societal Importance of the Research Achievements |
Dowling-Degos diseaseは点状もしくは網状の色素斑が腋窩や肘窩、首などの間擦部に出現する常染色体優性遺伝形式の遺伝性色素異常症ですが、治療法がまだありません。常染色体優性遺伝形式のため、患者さんは次世代への遺伝も1／2で起こるため、心理的な負担が大きく、そのため、患者さんやその家族は長年治療法を待ち望んでいます。本研究によって本疾患の病態解明や治療法の端緒となる可能性があります。
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