Pathophysiology of porokeratosis and cell competition in human

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03704
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kobe University (2021-2022); Keio University (2020)
• Principal Investigator: Kubo Akiharu 神戸大学, 医学研究科, 教授 (70335256)
• Co-Investigator(Kenkyū-buntansha): 福本 毅 神戸大学, 医学部附属病院, 助教 (80778770) ; 高橋 勇人 慶應義塾大学, 医学部(信濃町), 講師 (40398615) ; 藤田 春美 慶應義塾大学, 医学部(信濃町), 特任助教 (30736971)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 細胞競合 / 汗孔角化症 / クローン性増殖 / 前癌状態

Outline of Final Research Achievements

A total of 58 cases of porokeratosis, including 46 cases of disseminated porokeratosis, 7 cases of Mibelli's classic porokeratosis, and 5 cases of linear porokeratosis, were accumulated to search for causative genetic alterations. Of the 46 cases of disseminated porokeratosis, 29 had germline pathogenic variations in MVD, 6 in MVK, and 7 in FDPS. Two of the five cases of linear porokeratosis had germline pathogenic variations in MVD. No pathogenic variations were found in the known causative genes in all 7 cases of Mibelli's classic porokeratosis, and after further analysis, we identified a novel causative gene X for porokeratosis. Immunostaining for the product of the novel causative gene X has demonstrated that the skin lesions of porokeratosis are caused by clonal proliferation of the gene cells. Mice deficient in the novel gene X have been generated, and a porokeratosis mouse model is now under development.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

汗孔角化症は未だ有効な治療方法が確立されておらず、新規治療法開発のために病態メカニズムの解明が待ち望まれている。我々は今回、汗孔角化症の新規原因遺伝子Xを同定し、汗孔角化症の皮疹が変異細胞のクローン性増殖により生じていることを初めて組織学的に証明した。この成果は、今後の治療法開発のための大きなヒントとなる。またモデルマウス開発が確実に進展しており、今後の病態解明と治療法開発のための基盤となることが期待できる。