title: Neurodegeneration with tau accumulation in a transgenic mouse expressing V337M human tau.
abstract: 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.
authors.affiliation: Laboratory for Alzheimer's Disease, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tanemura
authors.forename: Miyuki
authors.initials: M
authors.lastname: Murayama
authors.forename: Takumi
authors.initials: T
authors.lastname: Akagi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hashikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Tominaga
authors.forename: Michinori
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D002452:Cell Count; D004396:Coloring Agents; D003224:Congo Red; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000145:classification / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D004396:Coloring Agents; D012333:RNA, Messenger; D016875:tau Proteins; D012967:Sodium Dodecyl Sulfate; D003224:Congo Red