Kampers T, Pangalos M, Geerts H, Wiech H, Mandelkow E
Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.
FEBS Lett. 1999 May 14;451(1):39-44. doi: 10.1016/s0014-5793(99)00522-0.
In Alzheimer's disease and related dementias, human tau protein aggregates into paired helical filaments and neurofibrillary tangles. However, such tau aggregates have not yet been demonstrated in transgenic mouse models of the disease. One of the possible explanations would be that mouse tau has different properties which prevents it from aggregating. We have cloned several murine tau isoforms, containing three or four repeats and different combinations of inserts, expressed them in Escherichia coli and show here that they can all be assembled into paired helical filaments similar to those in Alzheimer's disease, using the same protocols as with human tau. Therefore, the absence of pathologically aggregated tau in transgenic mice cannot be explained by intrinsic differences in mouse tau protein and instead must be explained by other as yet unknown factors.
在阿尔茨海默病及相关痴呆症中，人类tau蛋白聚集成双螺旋丝和神经原纤维缠结。然而，在该疾病的转基因小鼠模型中尚未证实存在此类tau聚集体。一种可能的解释是，小鼠tau具有不同特性，使其无法聚集。我们克隆了几种包含三个或四个重复序列以及不同插入片段组合的鼠tau异构体，在大肠杆菌中表达它们，并在此表明，使用与人类tau相同的实验方案，它们都能组装成与阿尔茨海默病中相似的双螺旋丝。因此，转基因小鼠中病理性聚集tau的缺失不能用小鼠tau蛋白的内在差异来解释，而必须用其他尚未知晓的因素来解释。
