Division of Experimental Animals, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Department of Nutritional Sciences, Nagoya University of Arts and Sciences, 57 Takenoyama, Iwasaki-cho, Nisshin, Aichi 470-0196, Japan.
Exp Anim. 2022 Nov 10;71(4):510-518. doi: 10.1538/expanim.22-0061. Epub 2022 Jul 28.
Various mouse models of type 2 diabetes have been established, but few of these show early onset and persistent hyperglycemia. We have established a congenic mouse strain (NSY.B6-Tyr,A) in which a spontaneous mutation of the agouti yellow (A) gene, which causes obesity by hyperphagia, was introduced into the NSY strain, which shows increased glucose intolerance with age. This strain has been maintained as a segregating inbred strain by mating obese yellow (A/a) males with normal black (a/a) females. All yellow males showed marked obesity and hyperglycemia (mean blood glucose level >400 mg/dl) from 10 to 24 weeks of age. The yellow males also showed glucose intolerance and insulin resistance. They provide a potentially valuable model mouse for research into type 2 diabetes, hyperlipidemia, fatty liver, and renal glomerular complications. Yellow female mice also showed marked obesity, but the incidence of diabetes and the severity of various pathological conditions were milder than in yellow males. None of the black mice showed hyperglycemia in either sex. NSY.B6-Tyr,A strain has good fertility and does not display inter-male aggression, making them useful as a new model for type 2 diabetes with early onset and persistent hyperglycemia.
已经建立了多种 2 型糖尿病的小鼠模型，但这些模型中很少有能表现出早期发病和持续高血糖的。我们建立了一个同源小鼠品系（NSY.B6-Tyr,A），在这个品系中，一个自发的 agouti 黄色（A）基因突变被引入 NSY 品系，该突变通过多食导致肥胖。随着年龄的增长，NSY 品系表现出葡萄糖耐量降低。该品系通过肥胖黄色（A/a）雄性与正常黑色（a/a）雌性交配，以分离的近交系形式维持。所有黄色雄性从 10 到 24 周龄时表现出明显的肥胖和高血糖（平均血糖水平>400mg/dl）。黄色雄性还表现出葡萄糖不耐受和胰岛素抵抗。它们为研究 2 型糖尿病、高脂血症、脂肪肝和肾脏肾小球并发症提供了一个有潜在价值的模型小鼠。黄色雌性小鼠也表现出明显的肥胖，但糖尿病的发病率和各种病理状况的严重程度比黄色雄性轻。在雄性和雌性中，没有黑色小鼠表现出高血糖。NSY.B6-Tyr,A 品系具有良好的繁殖力，且不会表现出雄性间的攻击行为，因此非常适合作为一种具有早期发病和持续高血糖的 2 型糖尿病新模型。
