Analyses of the onset mechanism of Schaaf-Yang syndrome

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15682
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Nagoya City University
• Principal Investigator: Yutaka Negishi 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (40798344)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: Schaaf-Yang症候群 / MAGEL2 / CRISPR/Cas9 / モデルマウス

Outline of Final Research Achievements

We generated genome-edited model that carried a truncating variant in Magel2 generated using the CRISPR/Cas9 system. The imprinted expression and spatial distribution of truncating Magel2 transcripts in the brain were maintained. Although neonatal mice were lighter than wildtype littermates, males and females weighed the same as their wildtype littermates by eight and four weeks of age, respectively. However, they did not show arthrogryposis and severe developmental delay. Collectively, the genome-edited mouse model maintains genomic imprinting and distribution of truncated Magel2 transcripts in the brain, but only partially recapitulates SYS phenotypes.

Free Research Field

小児科

Academic Significance and Societal Importance of the Research Achievements

本研究では、Schaaf-Yang症候群（SYS)患者のモデルとなるフレームシフト変異によるモデルマウスの作成に世界に先駆けて成功した。主に乳児期のみに哺乳不良が認められるSYSのヒトでの表現型を再現できたが、関節拘縮や重度精神運動発達遅滞は再現できなかった。表現型の一部しか示せず、治療法に関する検討まではできなかったが、新しいモデルマウスはSYSの病態解明に重要な役割を果たすことが期待できると考えられ、学術的意義は大きいと考えられた。