PMID- 16219306
OWN - NLM
STAT- MEDLINE
DCOM- 20051219
LR  - 20131121
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 579
IP  - 25
DP  - 2005 Oct 24
TI  - Transgenic mice expressing mutant (N279K) human tau show mutation dependent 
      cognitive deficits without neurofibrillary tangle formation.
PG  - 5704-12
AB  - Mutations in the tau gene, which is located on chromosome 17, were found 
      causative for autosomal dominantly inherited frontotemporal dementia and 
      parkinsonism linked to chromosome 17 (FTDP-17). To determine if cognitive 
      deficits could be caused by tau mutations, two transgenic mouse lines were 
      generated expressing a four-repeat isoform of human tau or its mutant, containing 
      one of the FTDP-17 mutations (WILD mice and N279K mice). In open field test, 
      N279K mice showed hyperactivity in locomotion and rearing. In prepulse inhibition 
      test, N279K mice but not Wild mice showed significant deficits. Both transgenic 
      mice, especially N279K mice, showed impairment in acquisition of spatial learning 
      in Morris water maze. Although both N279K mice and Wild mice acquired passive 
      avoidance as well as non-transgenic mice, N279K mice but not Wild mice showed 
      severe deficits in acquisition of active avoidance. Histological analysis of the 
      present mutant mice did not show any signs of neurofibrillary tangle formations 
      in the brain, and cognitive dysfunction seemed to precede such neuropathological 
      changes or occur independently from them. The behavioral phenotype of N279K mice 
      mimics features of human FTDP-17 and provides a basic model for elucidating 
      mechanisms underlying cognitive deficits in not only FTDP-17, but also diverse 
      tauopathies.
FAU - Taniguchi, Taizo
AU  - Taniguchi T
AD  - Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, 
      Nada-ku, Japan. tanigu@kobe-u.ac.jp
FAU - Doe, Nobutaka
AU  - Doe N
FAU - Matsuyama, Shogo
AU  - Matsuyama S
FAU - Kitamura, Yoshihisa
AU  - Kitamura Y
FAU - Mori, Hiroshi
AU  - Mori H
FAU - Saito, Naoaki
AU  - Saito N
FAU - Tanaka, Chikako
AU  - Tanaka C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051005
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (MAPT protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (tau Proteins)
RN  - 7006-34-0 (Asparagine)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Alzheimer Disease/*genetics/pathology
MH  - Animals
MH  - Asparagine/genetics
MH  - Avoidance Learning
MH  - Chromosomes, Human, Pair 17
MH  - Cognition Disorders/*genetics
MH  - *Disease Models, Animal
MH  - Hippocampus/chemistry
MH  - Humans
MH  - Lysine/genetics
MH  - Maze Learning
MH  - Mice
MH  - Mice, Transgenic/*genetics
MH  - Mutation, Missense
MH  - Nerve Tissue Proteins/analysis/*genetics/metabolism
MH  - Neurofibrillary Tangles/pathology
MH  - Phosphorylation
MH  - tau Proteins
EDAT- 2005/10/13 09:00
MHDA- 2005/12/20 09:00
CRDT- 2005/10/13 09:00
PHST- 2005/08/12 00:00 [received]
PHST- 2005/09/09 00:00 [accepted]
PHST- 2005/10/13 09:00 [pubmed]
PHST- 2005/12/20 09:00 [medline]
PHST- 2005/10/13 09:00 [entrez]
AID - S0014-5793(05)01168-3 [pii]
AID - 10.1016/j.febslet.2005.09.047 [doi]
PST - ppublish
SO  - FEBS Lett. 2005 Oct 24;579(25):5704-12. doi: 10.1016/j.febslet.2005.09.047. Epub 
      2005 Oct 5.