Mackay I R, Bone A, Tuomi T, Elliott R, Mandel T, Karopoulos C, Rowley M J
Centre for Molecular Biology and Medicine, Monash University, Clayton, Australia.
J Autoimmun. 1996 Dec;9(6):705-11. doi: 10.1006/jaut.1996.0092.
Spontaneous insulitis with insulin-dependent diabetes mellitus (IDDM) in rodent models, the BB rat and NOD mouse, has clarified the pathogenesis of and guided decisions on interventional therapy for human IDDM. However, the occurrence in such models of a standard marker of human IDDM, autoantibodies to beta islet cell constituents, has been controversial. Hence we assessed diabetes-prone rodents for the frequencies of raised levels of auto-antibodies to glutamic acid decarboxylase GAD (anti-GAD), insulin and heat shock protein 65 (HSP-65) in relation to levels in non-diabetes-prone animals and levels in human diabetic sera. Assays were performed sequentially at various ages of life. The immunoassays used for anti-GAD and anti-insulin were those validated for sensitivity and specificity for detection of the corresponding autoantibodies in human IDDM sera at international workshops. Positive controls included human IDDM sera with reactivity with GAD or insulin and, for mouse anti-GAD, the highly reactive monoclonal antibody, GAD-6. The results were that levels of autoantibodies in diabetes-prone BB rats or NOD mice to the "IDDM-relevant' autoantigens in our panel did not exceed levels in control rats or mice, and were much lower than levels in humans with IDDM. We conclude that the BB rat and NOD mouse represent a model, but not a facsimile, of human IDDM and that therapeutic successes in such models should be interpreted with caution in relation to interventional therapy for human IDDM.
在啮齿动物模型（BB大鼠和非肥胖糖尿病小鼠）中，胰岛素依赖型糖尿病（IDDM）的自发性胰岛炎阐明了人类IDDM的发病机制，并为其介入治疗的决策提供了指导。然而，在这些模型中出现人类IDDM的标准标志物——针对β胰岛细胞成分的自身抗体，一直存在争议。因此，我们评估了易患糖尿病的啮齿动物中谷氨酸脱羧酶GAD（抗GAD）、胰岛素和热休克蛋白65（HSP - 65）自身抗体水平升高的频率，并将其与不易患糖尿病的动物以及人类糖尿病血清中的水平进行比较。在动物生命的不同年龄段依次进行检测。用于抗GAD和抗胰岛素的免疫测定方法是在国际研讨会上针对检测人类IDDM血清中相应自身抗体的敏感性和特异性进行验证的。阳性对照包括与GAD或胰岛素有反应性的人类IDDM血清，对于小鼠抗GAD，使用高反应性单克隆抗体GAD - 6。结果显示，易患糖尿病的BB大鼠或非肥胖糖尿病小鼠针对我们检测组中“与IDDM相关”自身抗原的自身抗体水平并未超过对照大鼠或小鼠中的水平，且远低于人类IDDM患者的水平。我们得出结论，BB大鼠和非肥胖糖尿病小鼠代表了人类IDDM的一种模型，但并非完全相同的复制品，并且在将这些模型中的治疗成功应用于人类IDDM的介入治疗时应谨慎解读。
