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

doi:10.1016/j.isci.2023.107036

What the BTBR/J mouse has taught us about diabetes and diabetic complications

iScience. 2023 Jun 7;26(7):107036. doi: 10.1016/j.isci.2023.107036. eCollection 2023 Jul 21.

Authors

Mark P Keller¹, Kelly L Hudkins², Anath Shalev³, Sushant Bhatnagar³, Melkam A Kebede⁴, Matthew J Merrins^{5

6}, Dawn Belt Davis^{5

6}, Charles E Alpers², Michelle E Kimple^{5

6}, Alan D Attie^{1

5

7}

Affiliations

¹ Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
² Department of Pathology, University of Washington Medical Center, Seattle, WA 98195, USA.
³ Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL 35294, UK.
⁴ School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Camperdown, Sydney, NSW 2006, Australia.
⁵ Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
⁶ William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
⁷ Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.

Abstract

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 Lep^ob mutation. We went on to discover that the BTBR-Lep^ob 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.

Keywords: Animal physiology; Human metabolism; Model organism.

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Review

Abstract

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