Mouse models of diabetic nephropathy

Charles E Alpers1, Kelly L Hudkins

  • 1Department of Pathology, University of Washington Medical Center, Seattle, Washington 98195, USA. calp@uw.edu

Abstract

Insights

Identifying effective diabetic nephropathy therapies is challenging due to a lack of ideal animal models. Current leading murine models include eNOS deficient, Akita, OVE26, and BTBR ob/ob mice for studying advanced disease.

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.