Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?
Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?
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DOI：
10.2337/db16-1551
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发表时间：
2017-06
期刊：
影响因子：
7.7
通讯作者：
Atkinson MA
中科院分区：
文献类型：
--
作者：
O'Kell AL;Wasserfall C;Catchpole B;Davison LJ;Hess RS;Kushner JA;Atkinson MA
尽管在人类和小鼠疾病模型中进行了数十年的研究，但我们对1型糖尿病发病机制的理解仍存在重大差距。此外，能够延迟或停止β细胞破坏的临床前努力的疗法的转化受到限制。因此，迫切需要确定反映人类疾病的替代动物模型。在某些情况下，犬胰岛素缺乏性糖尿病被认为遵循自身免疫发病机制，与NOD小鼠和人类相似，其特征在于需要终身外源性胰岛素治疗的高血糖症。与人类1型糖尿病相似，典型的犬疾病似乎正在流行。尽管啮齿类动物的胰岛结构与人类明显不同，但犬胰腺内分泌细胞分布更相似。品种易感性的差异以及与MHC和其他犬免疫应答基因的相关性与人群中不同种族的差异平行，这是NOD小鼠的潜在益处。环境对疾病发展的影响也有利于犬科动物模型。在此，我们认为犬糖尿病有可能在胰腺组织病理学、β细胞功能和质量受损、胰岛炎症（即，胰岛炎）和β细胞抗原特异性自身抗体。
Despite decades of research in humans and mouse models of disease, substantial gaps remain in our understanding of pathogenic mechanisms underlying the development of type 1 diabetes. Furthermore, translation of therapies from preclinical efforts capable of delaying or halting β-cell destruction has been limited. Hence, a pressing need exists to identify alternative animal models that reflect human disease. Canine insulin deficiency diabetes is, in some cases, considered to follow autoimmune pathogenesis, similar to NOD mice and humans, characterized by hyperglycemia requiring lifelong exogenous insulin therapy. Also similar to human type 1 diabetes, the canonical canine disorder appears to be increasing in prevalence. Whereas islet architecture in rodents is distinctly different from humans, canine pancreatic endocrine cell distribution is more similar. Differences in breed susceptibility alongside associations with MHC and other canine immune response genes parallel that of different ethnic groups within the human population, a potential benefit over NOD mice. The impact of environment on disease development also favors canine over rodent models. Herein, we consider the potential for canine diabetes to provide valuable insights for human type 1 diabetes in terms of pancreatic histopathology, impairment of β-cell function and mass, islet inflammation (i.e., insulitis), and autoantibodies specific for β-cell antigens.