Mouse models of diabetic nephropathy

Area of Science:

• Nephrology
• Diabetology
• Animal Models

Background:

• Effective therapies for diabetic nephropathy are limited by the absence of ideal animal models.
• Murine models are crucial for understanding and developing treatments for diabetic kidney disease.

Purpose of the Study:

• To review the current status of leading murine models for diabetic nephropathy.
• To identify the most suitable animal models for studying advanced diabetic kidney disease and testing therapeutic interventions.

Main Methods:

• Review of existing literature and consensus guidelines for validating diabetic nephropathy models.
• Analysis of specific murine models, including those with endothelial nitric oxide synthase (eNOS) deficiency, Type I diabetes mutations (Akita, OVE26), and Type II diabetes (BTBR ob/ob).

Main Results:

• The Animals Models of Diabetic Complications Consortium provides guidelines for model validation.
• Murine models with eNOS deficiency, Akita, OVE26, and BTBR ob/ob mice exhibit key features of diabetic nephropathy.
• The BTBR ob/ob mouse shows early podocyte loss and mesangiolysis, characteristic of human diabetic nephropathy.

Conclusions:

• Few murine models develop advanced diabetic nephropathy lesions beyond mesangial matrix expansion.
• Mice with eNOS deficiency, OVE26, and BTBR ob/ob mice are currently the best models for advanced diabetic nephropathy.
• The BTBR ob/ob mouse is particularly valuable for testing interventions targeting podocyte loss and regeneration in diabetic nephropathy.