2019 Fiscal Year Final Research Report
Revertant mosaicism in congenital ichthyoses
Project/Area Number |
17H06271
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Research Category |
Grant-in-Aid for Challenging Research (Pioneering)
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Allocation Type | Single-year Grants |
Research Field |
Organ-based internal medicine and related fields
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Research Institution | Hokkaido University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
乃村 俊史 北海道大学, 大学病院, 講師 (50399911)
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Project Period (FY) |
2017-06-30 – 2020-03-31
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Keywords | 先天性魚鱗癬 |
Outline of Final Research Achievements |
In this study, we demonstrated that homologous recombination underlies reversion of pathogenic mutations in ichthyosis with confetti. We also showed that loricrin keratoderma represents revertant mosaicism. Although the precise mechanisms underlying reversion of mutations remain unclear, we demonstrated that (1) mutant protein does not increase DNA double strand break (DSB), (2) mutant protein does not affect the pathway choice in the repair of DSB induced by X-ray irradiation, (3) mutant protein does not increase replication stress, and (4) mutant protein alters replication stress response.
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Free Research Field |
皮膚科学
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Academic Significance and Societal Importance of the Research Achievements |
遺伝性疾患は、極めて難治性で新規治療法の開発が強く希求されている。遺伝性角化症は稀な疾患ではあるが、変異タンパク質が相同組換えを誘発する機構、すなわち病因遺伝子変異が自然に消失するメカニズムを解明できれば、遺伝性疾患全般の治療に広く応用できる可能性がある。人為的に相同組換えを誘導することで病因変異を消失させることができれば、これまで有効な治療法が存在しなかった疾患に対する新規治療法の開発が期待できるはずである。
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