Establishment of a novel early-onset diabetes model in house musk shrew (Suncus murinus)

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06401
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Nippon Veterinary and Life Science University
• Principal Investigator: Sasaki Noriyasu 日本獣医生命科学大学, 獣医学部, 准教授 (20307979)
• Co-Investigator(Kenkyū-buntansha): 金田 剛治 日本獣医生命科学大学, 獣医学部, 教授 (10350175) ; 神田 秀憲 日本獣医生命科学大学, 獣医学部, 助教 (30825609)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: スンクス / 早期発症糖尿病 / FOXO1 / FOXO6 / モデル動物

Outline of Final Research Achievements

The objective of this study was to explore the pathogenesis of non-obese early onset diabetis (EDS) Suncus (Suncuns murinus). To generate a new diabetic Suncus (EDBK) strain with matched genetic backgrounds, we repeated crosses breed of EDS with normal BK strain.
Sequence analysis of the transcription factor FOXO1, which is involved in pancreatic beta cell differentiation and dedifferentiation, in suncus revealed a high degree of conservation with over 90% homology to many previously reported mammalian FOXO1s, indicating significant preservation. FOXO6, which is involved in the regulation and expression of gluconeogenesis-related genes in the liver, was also found to be highly conserved.
Our study provided valuable insights into the pathophysiological mechanisms underlying non-obese early-onset type 2 diabetes, utilizing a unique novel animal model.

Free Research Field

獣医生化学

Academic Significance and Societal Importance of the Research Achievements

早期発症糖尿病スンクス（EDS）は非肥満型で、成長にともない症状が寛解する珍しい自然発生２型糖尿病モデル動物であるが、正常な対照系統が入手しにくいため利用されていなかった。そこで本研究では、交配により正常なスンクス（BK）の遺伝的背景を持った新たな早期糖尿病発症スンクス（EDBK）系統を作出し、このEDBK スンクスでの病態解明に取り組んだ。一般的に動物食性（肉食性）のモデル動物が少ないことから、本研究の知見は生物学、医学、獣医学と幅広い分野での応用が可能であり、特に2型糖尿病病態解明のモデルに適していると考えられる。