Genotype-phenotype analysis in recessive dystrophic epidermolysis bullosa using single cell analysis and mouse models

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08324
• 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: Osaka University
• Principal Investigator: Shimbo Takashi 大阪大学, 大学院医学系研究科, 特任准教授(常勤) (70780609)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: シングルセル解析 / 劣性栄養障害型表皮水疱症 / 遺伝子型-表現型相関

Outline of Final Research Achievements

Recessive dystrophic epidermolysis bullosa (RDEB) is one of the most severe forms of epidermolysis bullosa caused by mutations in the COL7A1 gene. Currently, there is no cure. This study aimed to clarify the correlation between the type of mutations found in the patients and the clinical manifestations. Through the establishments of mouse models with the patient derived mutations, and by performing single-cell RNA/chromatin analyses, we were able to understand skin homeostasis is disrupted in RDEB, at the molecular level in this disease.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

本研究では、マウスモデルを用いた遺伝子型-表現型相関に基づく病態予測の可能性を探究した。特に、遺伝病や希少遺伝性難病において、遺伝子変異の種類と病態・予後の正確な関連付けのための基盤研究を展開した。この研究成果は、劣性栄養障害型表皮水疱症患者に対する適切な治療方針の決定の助けとなる。さらに、本手法は他の遺伝病にも応用可能であり、難病治療戦略の向上に寄与する可能性があり社会的意義も非常に大きい。