Journal Article

Impairments in impulse control in mice transgenic for the human FTDP-17 tau<sub>V337M</sub> mutation are exacerbated by age

Sarah L. Lambourne, Trevor Humby, Anthony R. Isles, Piers C. Emson, Maria G. Spillantini and Lawrence S. Wilkinson

in Human Molecular Genetics

Volume 16, issue 14, pages 1708-1719
Published in print July 2007 | ISSN: 0964-6906
Published online May 2007 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddm119
Impairments in impulse control in mice transgenic for the human FTDP-17 tauV337M mutation are exacerbated by age

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Abnormalities in microtubule-associated tau protein are a key neuropathological feature of both Alzheimer's disease and many frontotemporal dementias (FTDs), including hereditary FTD with Parkinsonism linked to chromosome 17 (FTDP-17). In these disorders, tau becomes aberrantly phosphorylated, leading to the development of filamentous neurofibrillary tangles in the brain. Here we report, in a longitudinal ageing study, the sensorimotor and cognitive assessment of transgenic mice expressing the human tauV337M (‘Seattle Family A’) FTDP-17 mutation, which we have previously shown to demonstrate abnormalities in brain tau phosphorylation. The data indicated highly specific effects of transgene expression on the ability to withhold responding in a murine version of the 5-choice serial reaction time task, behaviour consistent with deficits in impulse control. Ageing exacerbated these effects. In young tauV337M mice, increased impulsivity was present under task conditions making inhibition of premature responding more difficult (longer inter-trial intervals) but not under baseline conditions. However, when older, the tauV337M mice showed further increases in premature responding, including under baseline conditions. These impulse control deficits were fully dissociable from sensorimotor or motivation effects on performance. The findings recapitulate core abnormalities in impulsive responding observed in both frontal variant FTD and FTDP-17 linked to the tauV337M mutation in humans.

Journal Article.  7353 words.  Illustrated.

Subjects: Genetics and Genomics

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