PMID- 15681835
OWN - NLM
STAT- MEDLINE
DCOM- 20050329
LR  - 20240412
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 166
IP  - 2
DP  - 2005 Feb
TI  - Accumulation of filamentous tau in the cerebral cortex of human tau R406W 
      transgenic mice.
PG  - 521-31
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-3beta 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).
FAU - Ikeda, Masaki
AU  - Ikeda M
AD  - Department of Neurology, Gunma University Graduate School of Medicine, 3-39-22 
      Showa-machi, Maebashi, Gunma 371-8511, Japan. mikeda@med.gunma-u.ac.jp
FAU - Shoji, Mikio
AU  - Shoji M
FAU - Kawarai, Toshitaka
AU  - Kawarai T
FAU - Kawarabayashi, Takeshi
AU  - Kawarabayashi T
FAU - Matsubara, Etsuro
AU  - Matsubara E
FAU - Murakami, Tetsuro
AU  - Murakami T
FAU - Sasaki, Atsushi
AU  - Sasaki A
FAU - Tomidokoro, Yasushi
AU  - Tomidokoro Y
FAU - Ikarashi, Yasushi
AU  - Ikarashi Y
FAU - Kuribara, Hisashi
AU  - Kuribara H
FAU - Ishiguro, Koichi
AU  - Ishiguro K
FAU - Hasegawa, Masato
AU  - Hasegawa M
FAU - Yen, Shu-Hui
AU  - Yen SH
FAU - Chishti, M Azhar
AU  - Chishti MA
FAU - Harigaya, Yasuo
AU  - Harigaya Y
FAU - Abe, Koji
AU  - Abe K
FAU - Okamoto, Koichi
AU  - Okamoto K
FAU - St George-Hyslop, Peter
AU  - St George-Hyslop P
FAU - Westaway, David
AU  - Westaway D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Prions)
RN  - 0 (Ubiquitin)
RN  - 0 (tau Proteins)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Amygdala/metabolism
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Behavior, Animal
MH  - Blotting, Western
MH  - Brain/metabolism
MH  - Cerebral Cortex/*metabolism
MH  - Cricetinae
MH  - Genetic Vectors
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Hippocampus/metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Microglia/metabolism
MH  - Microscopy, Electron
MH  - Mutation
MH  - Mutation, Missense
MH  - Phosphorylation
MH  - Prions/metabolism
MH  - Protein Conformation
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Transgenes
MH  - Ubiquitin/metabolism
MH  - tau Proteins/*biosynthesis/*genetics
PMC - PMC1602315
EDAT- 2005/02/01 09:00
MHDA- 2005/03/30 09:00
PMCR- 2005/08/01
CRDT- 2005/02/01 09:00
PHST- 2005/02/01 09:00 [pubmed]
PHST- 2005/03/30 09:00 [medline]
PHST- 2005/02/01 09:00 [entrez]
PHST- 2005/08/01 00:00 [pmc-release]
AID - S0002-9440(10)62274-2 [pii]
AID - 10.1016/S0002-9440(10)62274-2 [doi]
PST - ppublish
SO  - Am J Pathol. 2005 Feb;166(2):521-31. doi: 10.1016/S0002-9440(10)62274-2.