TY - JOUR
T1 - Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice
AU - Ikeda, Masaki
AU - Shoji, Mikio
AU - Kawarai, Toshitaka
AU - Kawarabayashi, Takeshi
AU - Matsubara, Etsuro
AU - Murakami, Tetsuro
AU - Sasaki, Atsushi
AU - Tomidokoro, Yasushi
AU - Ikarashi, Yasushi
AU - Kuribara, Hisashi
AU - Ishiguro, Koichi
AU - Hasegawa, Masato
AU - Yen, Shu Hui
AU - Chishti, M. Azhar
AU - Harigaya, Yasuo
AU - Abe, Koji
AU - Okamoto, Koichi
AU - St. George-Hyslop, Peter
AU - Westaway, David
N1 - Funding Information:
Supported by Scientific Research on Priority Areas (C)-Advanced Brain Science Project-(M.I. no. 15016018 ) and Grants-in-Aid for Scientific Research (C) (2) (M.I. no. 15590879 ), Grants-in-Aid for Primary Amyloidosis Research Committee (M.S.), and by Grants-in-Aid for Scientific Research (B) (M.S. no. 16390251 ) and Scientific Research on Priority Areas (C)-Advanced Brain Science Project-(M.S.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, the Canadian Institutes for Health Research, the Howard Hughes Medical Institute, the Canadian Genetic Diseases Network, and the Alzheimer Society of Ontario (P.S.G.-H.).
PY - 2005/2
Y1 - 2005/2
N2 - Missense mutations of the tau gene cause autosomal dominant frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an illness characterized by progressive personality changes, dementia, and parkinsonism. There is prominent frontotemporal lobe atrophy of the brain accompanied by abundant tau accumulation with neurofibrillary tangles and neuronal cell loss. Using a hamster prion protein gene expression vector, we generated several independent lines of transgenic (Tg) mice expressing the longest form of the human four-repeat tau with the R406W mutation associated with FTDP-17. The TgTauR406W 21807 line showed tau accumulation beginning in the hippocampus and amygdala at 6 months of age, which subsequently spread to the cortices and subcortical areas. The accumulated tau was phosphorylated, ubiquitinated, conformationally changed, argyrophilic, and sarcosyl-insoluble. Activation of GSK-3β and astrocytic induction of mouse tau were observed. Astrogliosis and microgliosis correlated with prominent tau accumulation. Electron microscopic examination revealed the presence of straight filaments. Behavioral tests showed motor disturbances and progressive acquired memory loss between 10 to 12 months of age. These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer's disease (AD).
AB - Missense mutations of the tau gene cause autosomal dominant frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an illness characterized by progressive personality changes, dementia, and parkinsonism. There is prominent frontotemporal lobe atrophy of the brain accompanied by abundant tau accumulation with neurofibrillary tangles and neuronal cell loss. Using a hamster prion protein gene expression vector, we generated several independent lines of transgenic (Tg) mice expressing the longest form of the human four-repeat tau with the R406W mutation associated with FTDP-17. The TgTauR406W 21807 line showed tau accumulation beginning in the hippocampus and amygdala at 6 months of age, which subsequently spread to the cortices and subcortical areas. The accumulated tau was phosphorylated, ubiquitinated, conformationally changed, argyrophilic, and sarcosyl-insoluble. Activation of GSK-3β and astrocytic induction of mouse tau were observed. Astrogliosis and microgliosis correlated with prominent tau accumulation. Electron microscopic examination revealed the presence of straight filaments. Behavioral tests showed motor disturbances and progressive acquired memory loss between 10 to 12 months of age. These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer's disease (AD).
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U2 - 10.1016/S0002-9440(10)62274-2
DO - 10.1016/S0002-9440(10)62274-2
M3 - Article
C2 - 15681835
AN - SCOPUS:19944432508
SN - 0002-9440
VL - 166
SP - 521
EP - 531
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -