Mechanism of lipid antigen presentation via CD1a and induction of skin inflammation

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K08310
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Tokyo Women's Medical University (2019-2023); Keio University (2018)
• Principal Investigator: Arao Noriko 東京女子医科大学, 医学部, 准教授 (80397629)
• Co-Investigator(Kenkyū-buntansha): 久保 亜紀子 神戸大学, 医学研究科, 特命講師 (50455573) ; 久保 亮治 慶應義塾大学, 医学部(信濃町), 准教授 (70335256)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: CHILD症候群 / 皮膚炎

Outline of Final Research Achievements

We successfully created skin epidermis-specific NSDHL conditional knockout mice (K5-Cre-NSDHLflox). NSDHL targeting vector was introduced into mouse ES cells via electroporation, followed by colony picking. After screening of ES cells, injection into blastocysts (BALB/c) was performed to generate NSDHL chimeric mice. Chimeric F1 mice (♂) with ES cells (black hair) and host embryos (BALB/c, albino) were crossed with B6 mice (black) and genotyped for 5 female F2 mice with black coat color. DNA was extracted from the tails of chimeric mice and genotyping was confirmed. Furthermore, NSDHL mutant mice carrying K5-Cre were generated by crossing NSDHL chimeric mice with K5-Cre, resulting in skin epidermis-specific NSDHL knockout.

Free Research Field

genetic skin diseases

Academic Significance and Societal Importance of the Research Achievements

表皮特異的NSDHLコンディショナルノックアウトマウス(K5-Cre-NSDHLflox)の作成することに成功した。表皮特異的NSDHLコンディショナルノックアウトマウスの皮膚にモザイク状に脱毛を伴うphenotypeが見られ、3匹のマウスについてその部位の皮膚を生検して、皮膚のHE染色を行った。脱毛部では表皮の菲薄化と毛包構造の消失があり、一方で有毛部では、皮膚炎を想起させる角質層の錯角化を認めた。今後、CHILD症候群における皮膚炎発症のメカニズム解明に有益な成果と考えられる。