Identification of a novel gene causing cholesterol synthesis deficiency

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10044
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: Kikuchi Atsuo 東北大学, 大学病院, 助教 (30447156)
• Co-Investigator(Kenkyū-buntansha): 仲川 清隆 東北大学, 農学研究科, 教授 (80361145)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 無毛症 / コレステロール合成経路 / 脂質代謝 / 新規病因遺伝子 / コンディショナルノックアウトマウス

Outline of Final Research Achievements

Skin lesions, cataracts, and congenital anomalies have been frequently associated with inherited deficiencies in enzymes that synthesize cholesterol, but most of the enzymes have not been reported in humans yet. We had identified a novel candidate gene, LSS, that encodes an enzyme of the same pathway in siblings with congenital hypotrichosis and multiple malformations. In this study, we attempted to genetically and functionally prove the LSS gene deficiency by generating three types of conditional knockout mice that presented skin barrier dysfunction, transient alopecia, and cataract, respectively, all of which reproduced the patient's phenotype. These mice will be useful for understanding the pathogenesis of LSS deficiency in the future.

Free Research Field

希少疾患

Academic Significance and Societal Importance of the Research Achievements

本研究ではヒトLSS欠損症の症状を再現するモデルマウスを作成することができた。またヒトやマウスの皮脂・皮膚を使った代謝産物の解析により本疾患における酵素ブロックの証明に成功した。本研究で作成したモデルマウスを用いた今後の研究によって、LSSが欠損した際の病態メカニズムのさらなる解明及び本症への治療法の開発につながることが期待される。