NOD Mice-Good Model for T1D but Not Without Limitations.

NOD Mice-Good Model for T1D but Not Without Limitations.
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DOI:
10.1177/0963689720939127
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发表时间:
2020-01
影响因子:
3.3
通讯作者:
Abdulreda MH
Abdulreda MH
中科院分区:
医学4区
文献类型:
--
作者:
Aldrich VR;Hernandez-Rovira BB;Chandwani A;Abdulreda MH

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1型糖尿病(T1D)的非肥胖糖尿病(NOD)小鼠模型是在20世纪80年代偶然发现的,此后被广泛用于T1D和糖尿病并发症的研究。目前的体内研究最初旨在前瞻性评估高血糖症发作是否与T1D进展期间易患糖尿病的雌性NOD小鼠中炎症损伤下β细胞的物理破坏或功能受损相关。将绿色荧光蛋白(GFP)表达的报告胰岛移植到糖尿病前期16至20周龄的NOD小鼠的眼前房(ACE)中,除了使用抗CD3单克隆抗体治疗进行免疫调节和不进行免疫调节外,还对ACE进行纵向监测。然而,针对表达GFP的β细胞存在早期且强烈的免疫反应,导致它们过早破坏,而与进展小鼠中的自身免疫性T1 D发展无关,最终成为高血糖。这种免疫反应也发生在非进展NOD受体中。这些发现显示了NOD小鼠对GFP的先前未知的反应,这阻止了本研究的原始目标的实现,但突出了NOD小鼠的一个新特征,在T1D研究中使用该模型设计实验时应考虑该特征。
The nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D) was discovered by coincidence in the 1980s and has since been widely used in the investigation of T1D and diabetic complications. The current in vivo study was originally designed to prospectively assess whether hyperglycemia onset is associated with physical destruction or functional impairment of beta cells under inflammatory insult during T1D progression in diabetes-prone female NOD mice. Prediabetic 16- to 20-wk-old NOD mice were transplanted with green fluorescent protein (GFP)-expressing reporter islets in the anterior chamber of the eye (ACE) that were monitored longitudinally, in addition to glycemia, with and without immune modulation using anti-CD3 monoclonal antibody therapy. However, there was an early and vigorous immune reaction against the GFP-expressing beta cells that lead to their premature destruction independent of autoimmune T1D development in progressor mice that eventually became hyperglycemic. This immune reaction also occurred in nonprogressor NOD recipients. These findings showed a previously unknown reaction of NOD mice to GFP that prevented achieving the original goals of this study but highlighted a new feature of the NOD mice that should be considered when designing experiments using this model in T1D research.
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