Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer’s disease-like pathology. Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer’s disease-like pathology

We generated knock-in mice that express wildtype human Aβ under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aβ sequence to its wild-type human counterpart leads to age-dependent impairments in cognition and synaptic plasticity, brain volumetric changes, inflammatory alterations, the appearance of Periodic Acid-Schiff (PAS) granules and changes in gene expression. Overall design: knock-in mouse model that expresses human non-mutated Aβ in the natural context of the endogenous mouse APP gene

我们构建了在小鼠App基因座调控下表达野生型人类Aβ的基因敲入（knock-in）小鼠。值得注意的是，将小鼠Aβ序列中的3个氨基酸替换为其野生型人类同源序列后，可引发年龄依赖性的认知与突触可塑性损伤、脑体积改变、炎症异常、过碘酸-希夫（Periodic Acid-Schiff, PAS）颗粒的出现以及基因表达变化。整体实验设计：该基因敲入小鼠模型可在内源性小鼠APP基因的天然调控背景下表达人源非突变型Aβ