Mechanistic insights of the pathogenesis of alopecia using a novel vitamin D-dependent richets mouse model

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19518
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: The University of Tokushima
• Principal Investigator: SAWATSUBASHI Shun 徳島大学, 先端酵素学研究所, 特任准教授 (70535103)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Keywords: ビタミンD / ビタミンD受容体 / 転写 / くる病 / 脱毛 / ゲノム編集 / 毛包 / 毛周期

Outline of Final Research Achievements

The hair follicle is a dynamically regenerating organ, and the hair cycle is an important model for regeneration research. In this study, we focused on the pathogenesis of hair loss in a vitamin D-dependent rickets model mouse, and aimed to clarify the regulatory mechanism of the catagen, which has not yet been elucidated.
As a result, we established a novel mouse model of rickets that mimics point mutations in human disease. Furthermore, we succeeded in establishing 10 strains of the VDR mutations using genome editing, and investigated the pathophisiology. Interestingly, each point-mutated VDR showed differences in the interacting proteins that reduced their binding ability. This is an important result to reconsider the conventional disease mechanism, in which the loss of interaction with RXR, a heterodimer of VDR, has been considered as the main cause.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

毛を生み出す毛包は、成長期・退縮期・休止期を周期的に繰り返す動的に維持された器官であり、幹細胞研究に用いられてきた。従来は発毛の観点で、どのように成長期が制御されるか、に主眼をおいた研究が展開されており、退縮期の制御に焦点を当てた研究は驚くほど少ない。本研究は、将来的な脱毛の治療法の開発を指向し、指定難病であるビタミンD依存性くる病でみられる禿頭や、加齢とともに生じる脱毛の原因を解明することを試みた。結果として、毛産生細胞が不要となったステージで、正しく消去される機構の重要性が見出され、その破綻の結果として残存する『居残り細胞』が病態を引き起こすという新たなモデルを創出することができた。