Development and analysis of a novel type 2 diabetic mouse model with kidney fibrosis can pursue pathology of diabetic nephropathy

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K18015
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Dokkyo Medical University
• Principal Investigator: Inoue Yuiko (水沼有威子) 獨協医科大学, 医学部, 助教 (80784008)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 2型糖尿病 / 線維化 / CD-1db/dbマウス / AcSDKP / 糖尿病腎症 / 戻し交配

Outline of Final Research Achievements

I've found that a novel type 2 diabetic mouse model (CD-1db/db) with progressive kidney fibrosis revealed fibrosis in heart and liver. Also, CD-1db/db mice showed atrophy of pancreatic islets and decreased levels of pancreatic beta cells. In this study, I aimed to establish the therapeutic target in type 2 diabetic nephropathy with analyzing the phenotype of CD-1db/db mice by comparing with diabetic db/db mice with a BKS background (BKSdb/db), commonly used as a type 2 diabetic mouse model, and analyzing the molecular mechanisms of type 2 diabetic nephropathy with experimental treatments to CD-1db/db mice.
BKSdb/m mice were backcrossed into CD-1 mice for 14 generations. By crossing 14th backcrossed CD-1db/m mice each other, I obtained enough 14th CD-1db/db mice. I can report that CD-1db/db mice have been established in my university finally.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

2022年時点の透析導入症例における原疾患のうち、糖尿病性腎症は38%を占めており、糖尿病性腎症の発症・進行を防ぐことの重要性は以前から強調されている。2型糖尿病に伴う腎障害の病理学的特徴として、糸球体病変を呈するもの、尿細管間質病変が顕著なもの、血管病変が進展した腎硬化症の特徴を有するものなど1型糖尿病に比し多岐にわたることが報告されている。2型糖尿病かつ腎線維化を呈するモデル動物は存在しなかったが、CD-1db/dbマウスがその役目を果たせると考えられ、CD-1db/dbマウスの詳細な解析や実験治療を行うことで、特異的治療法の存在しない腎症に対する新たな治療戦略の創出につながると考える。