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Development of the Nonobese Diabetic Mouse and Contribution of Animal Models for Understanding Type 1 Diabetes

Mullen, Yoko MD, PhD

doi: 10.1097/MPA.0000000000000828

In 1974, the discovery of a mouse and a rat that spontaneously developed hyperglycemia led to the development of 2 autoimmune diabetes models: nonobese diabetic (NOD) mouse and Bio-Breeding rat. These models have contributed to our understanding of autoimmune diabetes, provided tools to dissect autoimmune islet damage, and facilitated development of early detection, prevention, and treatment of type 1 diabetes. The genetic characterization, monoclonal antibodies, and congenic strains have made NOD mice especially useful.

Although the establishment of the inbred NOD mouse strain was documented by Makino et al (Jikken Dobutsu. 1980;29:1–13), this review will focus on the not-as-well-known history leading to the discovery of a glycosuric female mouse by Yoshihiro Tochino. This discovery was spearheaded by years of effort by Japanese scientists from different disciplines and dedicated animal care personnel and by the support of the Shionogi Pharmaceutical Company, Osaka, Japan. The history is based on the early literature, mostly written in Japanese, and personal communications especially with Dr Tochino, who was involved in diabetes animal model development and who contributed to the release of NOD mice to the international scientific community. This article also reviews the scientific contributions made by the Bio-Breeding rat to autoimmune diabetes.

From the Department of Translational Research and Cellular Therapeutics, Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA.

Received for publication October 27, 2016; accepted January 10, 2017.

Address correspondence to: Yoko Mullen, MD, PhD, Department of Diabetes and Metabolic Disease Research, Beckman Research Institute of City of Hope, 1500 E Duarte Rd, Duarte, CA 91010 (e-mail:

This study was supported by a grant from the Nora Eccles Treadwell Foundation.

The author declares no conflict of interest.

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