A transgenic rat model of Alzheimer's disease with extracellular Aβ deposition
A transgenic rat model of Alzheimer's disease with extracellular Aβ deposition
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DOI：
10.1016/j.neurobiolaging.2007.10.006
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发表时间：
2009-07-01
影响因子：
4.2
通讯作者：
Howland, David S.
中科院分区：
文献类型：
--
作者：
Flood, Dorothy G.;Lin, Yin-Guo;Howland, David S.
许多沉积淀粉样蛋白（A - β）的阿尔茨海默病（AD）转基因小鼠模型已经产生，但A - β沉积大鼠模型的开发尚未成功。在这里，我们描述了细胞外纤维a β沉积的大鼠模型。用表达AD家族性突变K670N/M671L和K670N/M671L/V717I的人淀粉样前体蛋白（APP）转基因大鼠进行杂交。在17-18个月大时，双纯合子大鼠的β产生足以沉积。通过将携带人存在素-1 （PS-1）转基因的第三个大鼠系与FAD M146V突变杂交，降低了A β沉积的发病年龄。三纯合子系在7月龄时开始A β沉积。沉积物与小鼠模型中观察到的相似，并显示出周围胶质细胞和磷酸化的tau反应性。ELISA测量的A - β水平与小鼠模型中报告的水平相当，这表明大鼠体内不需要大量的可溶性A - β来产生A - β沉积。(C) 2007爱思唯尔公司版权所有。
Many transgenic mouse models of Alzheimer's disease (AD) that deposit amyloid (A beta) have been produced, but development of an A beta-depositing rat model has not been successful. Here, we describe a rat model with extracellular fibrillar A beta deposition. Two lines of Sprague Dawley rats with transgenes expressing human amyloid precursor protein (APP) with the familial AD (FAD) mutations K670N/M671L and K670N/M671L/V717I were crossed. A beta production in the double homozygous rats was sufficient for deposition by 17-18 months of age. The age of onset of A beta deposition was reduced by crossing in a third rat line carrying a human presenitin-1 (PS-1) transgene with the FAD M146V mutation. The triple homozygous line had an onset of A beta deposition by 7 months of age. Deposits appeared similar to those observed in the mouse models and displayed surrounding glial and phosphorylated tau reactivity. A beta levels measured by ELISA were comparable to those reported in mouse models, suggesting that substantially greater amounts of soluble A beta are not required in the rat to generate A beta deposition. (C) 2007 Elsevier Inc. All rights reserved.