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Transgenic mice expressing mutant (N279K) human tau show mutation dependent cognitive deficits without neurofibrillary tangle formation
Author(s) -
Taniguchi Taizo,
Doe Nobutaka,
Matsuyama Shogo,
Kitamura Yoshihisa,
Mori Hiroshi,
Saito Naoaki,
Tanaka Chikako
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.09.047
Subject(s) - genetically modified mouse , mutant , neuroscience , frontotemporal dementia , transgene , tau protein , prepulse inhibition , morris water navigation task , biology , parkinsonism , alzheimer's disease , psychology , pathology , genetics , dementia , cognition , medicine , gene , disease , schizophrenia (object oriented programming) , psychiatry
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.