What the BTBR/J mouse has taught us about diabetes and diabetic complications
Mark P. Keller,
Kelly L. Hudkins,
Anath Shalev,
Sushant Bhatnagar,
Melkam A. Kebede,
Matthew J. Merrins,
Dawn Belt Davis,
Charles E. Alpers,
Michelle E. Kimple,
Alan D. Attie
Affiliations
Mark P. Keller
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA
Kelly L. Hudkins
Department of Pathology, University of Washington Medical Center, Seattle, WA 98195, USA
Anath Shalev
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL 35294, UK
Sushant Bhatnagar
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL 35294, UK
Melkam A. Kebede
School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Camperdown, Sydney, NSW 2006, Australia
Matthew J. Merrins
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA
Dawn Belt Davis
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA
Charles E. Alpers
Department of Pathology, University of Washington Medical Center, Seattle, WA 98195, USA
Michelle E. Kimple
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA
Alan D. Attie
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Corresponding author
Summary: Human and mouse genetics have delivered numerous diabetogenic loci, but it is mainly through the use of animal models that the pathophysiological basis for their contribution to diabetes has been investigated. More than 20 years ago, we serendipidously identified a mouse strain that could serve as a model of obesity-prone type 2 diabetes, the BTBR (Black and Tan Brachyury) mouse (BTBR T+ Itpr3tf/J, 2018) carrying the Lepob mutation. We went on to discover that the BTBR-Lepob mouse is an excellent model of diabetic nephropathy and is now widely used by nephrologists in academia and the pharmaceutical industry. In this review, we describe the motivation for developing this animal model, the many genes identified and the insights about diabetes and diabetes complications derived from >100 studies conducted in this remarkable animal model.
