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The Journal of Neuroscience, January 1, 2002, 22(1):133-141

Neurodegeneration with Tau Accumulation in a Transgenic Mouse Expressing V337M Human Tau

Kentaro Tanemura1, Miyuki Murayama1, Takumi Akagi2, Tsutomu Hashikawa2, Takashi Tominaga3, Michinori Ichikawa3, Haruyasu Yamaguchi4, and Akihiko Takashima1

1 Laboratory for Alzheimer's Disease, 2 Neural Architecture, and 3 Brain Operative Device, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan, and 4 Gunma University School of Health Sciences, Gunma 371-8511, Japan

Formation of neurofibrillary tangles (NFTs) is a common neuropathological feature found in several neurodegenerative diseases, including Alzheimer's disease. We have developed a transgenic (Tg) mouse expressing mutant human tau (V337M), derived from frontotemporal dementia parkinsonism-17. V337M Tg mice revealed tau aggregations in the hippocampus, which fulfills the histological criteria for NFTs in human neurodegenerative diseases. Concurrent with the accumulation of RNA and phosphorylated tau, neurons exhibited morphological characteristics of degenerating neurons, which include a loss of microtubules, accumulation of ribosomes, plasma and nuclear membrane ruffling, and swelling of the Golgi network. Thus, mutant tau induces neuronal degeneration associated with the accumulation of RNA and phosphorylated tau. The functional consequences of this neuronal degeneration was evidenced by the reduction of hippocampal neural activity and behavioral abnormality in Tg mice.

Key words: neurodegeneration; phosphorylated tau; RNA; NFT; Tg mouse; FTDP-17


Copyright © 2002 Society for Neuroscience  0270-6474/02/221133-09$05.00/0


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