| Project/Area Number |
20K17306
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Yamagata University |
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Principal Investigator |
ARAKI Yuta 山形大学, 医学部, 助教 (30637228)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | SASH1 / 遺伝性色素異常症 / モデルマウス / 機能解析 / CRISPR/Cas9 / ロドデノール |
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| Outline of Research at the Start |
SASH1遺伝子の変異が原因と考えられる新たな色素異常症がこの数年でいくつか報告されており、我々の施設でもこれらの報告例と類似した臨床所見を示す同遺伝子の変異症例を複数例経験している。しかし、モデルマウス等を使用したin vivoでの研究はなされておらず、病態や遺伝子の機能はいまだ十分に明らかにされていない。
本研究では、同遺伝子のノックアウトマウス、さらに変異を組み込んだ疾患モデルマウスを作製し、SASH1遺伝子変異による遺伝性色素異常症の病態解明と機能解析を行う。
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| Outline of Final Research Achievements |
Using the CRISPR/Cas9 system, SASH1 gene mutant mice were established and crossed with Japanese skin-colored mice to establish model mice with pigmented epidermis. Although no pigmented spots similar to those seen in patients were observed, dermoscopy revealed that the area of pigmented spots around pores was uneven. When the skin tissue was examined, there were few dendrites extending from melanocytes, and the number of melanocytes around pores varied. When depigmentation was induced and the process of pigment regeneration was observed, many melanocytes were found around pores, and their number tended to increase with pigment regeneration. From the above, it was suggested that there was an abnormal distribution of melanocytes around pores in the model mice, which may be involved in the formation of the disease.
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| Academic Significance and Societal Importance of the Research Achievements |
SASH1遺伝子変異による遺伝性色素異常症は、近年、遺伝性汎発性色素異常症（DUH）として扱われている。しかし、その臨床症状は従来のDUHとは少し異なっており、未だ発症機序やSASH1遺伝子の機能解析は十分には進んでいない。患者数は少ないが、日本を含めアジア地域での報告が多く、病態の解明が必要とされる疾患である。病態解明に向けた今後の研究の為にも、本研究でモデルマウスを作製できたことの意義は大きいと考える。
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