Formation of filamentous tau aggregations in transgenic mice expressing V337M human tau.
Formation of neurofibrillary tangles (NFTs) is the most common feature in several neurodegenerative diseases, including Alzheimer's disease (AD). Here we report the formation of filamentous tau aggregations having a beta-sheet structure in transgenic mice expressing mutant human tau. These mice contain a tau gene with a mutation of the frontotemporal dementia parkinsonism (FTDP-17) type, in which valine is substituted with methionine residue 337. The aggregation of tau in these transgenic mice satisfies all histological criteria used to identify NFTs common to human neurodegenerative diseases. These mice, therefore, provide a preclinical model for the testing of therapeutic drugs for the treatment of neurodegenerative disorders that exhibit NFTs.
Tanemura
K
K
Laboratory for Alzheimer's Disease, Neural Architecture, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.
Akagi
T
T
Murayama
M
M
Kikuchi
N
N
Murayama
O
O
Hashikawa
T
T
Yoshiike
Y
Y
Park
J M
JM
Matsuda
K
K
Nakao
S
S
Sun
X
X
Sato
S
S
Yamaguchi
H
H
Takashima
A
A
D000818:Animals; D052160:Benzothiazoles; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004396:Coloring Agents; D003224:Congo Red; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D020125:Mutation, Missense / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D017433:Protein Structure, Secondary / Q000235:genetics; D013844:Thiazoles; D014162:Transfection / Q000379:methods; D025801:Ubiquitin / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
D052160:Benzothiazoles; D004396:Coloring Agents; D013844:Thiazoles; D025801:Ubiquitin; D016875:tau Proteins; C009462:thioflavin T; D003224:Congo Red