UP FRONT MATTERS: Special Article

Mouse Models of Diabetic Nephropathy

Frank C. Brosius III ^*1, Charles E. Alpers , Erwin P. Bottinger , Matthew D. Breyer , Thomas M. Coffman ^||, Susan B. Gurley ^||, Raymond C. Harris ^¶, Masao Kakoki ^**, Matthias Kretzler ^*, Edward H. Leiter , Moshe Levi , Richard A. McIndoe , Kumar Sharma ^||||, Oliver Smithies ^**, Katalin Susztak ^¶¶, Nobuyuki Takahashi ^**, Takamune Takahashi ^¶, and for the Animal Models of Diabetic Complications Consortium

*Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan; Department of Pathology, University of Washington, Seattle, Washington; Charles R. Bronfman Institute for Personalized Medicine, Mount Sinai School for Medicine, New York, New York; Biotechnology Discovery Research, Lilly Research Laboratories, Indianapolis, Indiana; ||Duke University and VA Medical Centers, Durham, North Carolina; ¶Department of Medicine, Vanderbilt University, Nashville, Tennessee; **Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; The Jackson Laboratory, Bar Harbor, Maine; Departments of Medicine, Physiology, and Biophysics, University of Colorado, Denver, Colorado; Center For Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, Georgia; ||||Center for Renal Translational Medicine, University of California San Diego/VA San Diego Health System, La Jolla, California; and ¶¶Department of Medicine, Albert Einstein College of Medicine, Bronx, New York

¹ To whom correspondence should be addressed. E-mail: fbrosius{at}umich.edu.

	Abstract

Diabetic nephropathy is a major cause of ESRD worldwide. Despite its prevalence, a lack of reliable animal models that mimic human disease has delayed the identification of specific factors that cause or predict diabetic nephropathy. The Animal Models of Diabetic Complications Consortium (AMDCC) was created in 2001 by the National Institutes of Health to develop and characterize models of diabetic nephropathy and other complications. This interim report and our online supplement detail the progress made toward that goal, specifically in the development and testing of murine models. Updates are provided on validation criteria for early and advanced diabetic nephropathy, phenotyping methods, the effect of background strain on nephropathy, current best models of diabetic nephropathy, negative models, and views of future directions. AMDCC investigators and other investigators in the field have yet to validate a complete murine model of human diabetic kidney disease. Nonetheless, the critical analysis of existing murine models substantially enhances our understanding of this disease process.