陶氏病
基因亚型
τ蛋白
生物
转基因小鼠
表型
细胞生物学
病态的
转基因
遗传学
神经退行性变
阿尔茨海默病
疾病
病理
基因
医学
作者
Zhuohao He,Jennifer D. McBride,Hong Xu,Lakshmi Changolkar,Soojung Kim,Bin Zhang,Sneha Narasimhan,Garrett S. Gibbons,Jing Guo,Michael Kozak,Gerard D. Schellenberg,John Q. Trojanowski,Virginia M.‐Y. Lee
标识
DOI:10.1038/s41467-019-13787-x
摘要
Abstract The deposition of pathological tau is a common feature in several neurodegenerative tauopathies. Although equal ratios of tau isoforms with 3 (3R) and 4 (4R) microtubule-binding repeats are expressed in the adult human brain, the pathological tau from different tauopathies have distinct isoform compositions and cell type specificities. The underlying mechanisms of tauopathies are unknown, partially due to the lack of proper models. Here, we generate a new transgenic mouse line expressing equal ratios of 3R and 4R human tau isoforms (6hTau mice). Intracerebral injections of distinct human tauopathy brain-derived tau strains into 6hTau mice recapitulate the deposition of pathological tau with distinct tau isoform compositions and cell type specificities as in human tauopathies. Moreover, through in vivo propagation of these tau strains among different mouse lines, we demonstrate that the transmission of distinct tau strains is independent of strain isoform compositions, but instead intrinsic to unique pathological conformations.
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