An attempt to improve pathology of muscular dystrophy model rats by preventing cellular senescence.

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14883
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Integrative animal science
• Research Institution: The University of Tokyo
• Principal Investigator: Yamanouchi Keitaro 東京大学, 大学院農学生命科学研究科(農学部), 准教授 (70272440)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 筋ジストロフィー / 骨格筋 / 筋再生 / 細胞老化 / 筋衛星細胞 / 間葉系前駆細胞 / ゲノム編集

Outline of Final Research Achievements

We previously succeeded in generating rats having out-of-frame mutation in dystrophin gene by genome editing. The rats show very severe phenotype in their skeletal muscle, which is similar to that seen in Duchenne muscular dystrophy patients. Since the expression of p16, a senescent cell marker, was up-regulated in skeletal muscle of dystrophin-mutated rats, we hypothesized cellular senescence is involved in the progression of skeletal muscle pathology. As a result, we found that TGF-β expression is increased in the skeletal muscle of dystrophin-mutated rats, and thus increased TGF-β induces cellular senescence in satellite cells.

Free Research Field

獣医生理学