Development and analysis of an animal model of Musculocontractral Ehlers-Danlos syndrome

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08745
• 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: Shinshu University
• Principal Investigator: Yoshizawa Takahiro 信州大学, 学術研究院総合人間科学系, 助教 (40713392)
• Co-Investigator(Kenkyū-buntansha): 古庄 知己 信州大学, 学術研究院医学系, 教授 (90276311) ; 水本 秀二 名城大学, 薬学部, 准教授 (40443973)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 疾患モデル動物 / 筋拘縮型エーラス・ダンロス症候群 / Chst14

Outline of Final Research Achievements

Musculocontractural Ehlers-Danlos Syndrome (mcEDS) shows some serious cutaneous symptoms with dermatan sulfate (DS) deficiency caused by mutations in CHST14 gene. In this study, Chst14 gene-deleted mice (Chst14 KO) were used as an animal model of mcEDS. Chst14 KO showed some cutaneous phenotypes such as deformations of collagen bundles and fibrils, mechanical weakness, and delay of wound healing which were similar to patients with mcEDS. Cell migration and proliferation were depressed in skin fibroblast of Chst14 KO. These results suggest that Chst14 gene affects structure and strength of extracellular matrix and cell migration and proliferation.

Free Research Field

病態医化学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、Chst14 KOがmcEDSの皮膚症状の疾患モデル動物として有用であることが示された。また、Chst14遺伝子やDSが、細胞外マトリックスの構造と強度の維持や、皮膚線維芽細胞の増殖と遊走に関与することが示唆され、mcEDSの病態メカニズム解明の糸口となることが期待された。