Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice

Tau, one of the major neuronal microtubule-associated proteins (MAPs), is i mportant for neuronal cell morphogenesis and axonal maintenance. Tau is als o known to be a component of the paired helical filaments (PHFs) in Alzheim er's disease patients. Recently, mutations in the tau gene were found in a hereditary neurodegenarative disease called frontotemporal dementia and par kinsonism linked to chromosome 17 (FTDP-17) which exhibits various neurolog ical and neuropathological characteristics including PHF-like intracellular tau deposit formation. Currently, the phenotype of the disease is thought to be due to: (1) the toxicity of mutant tau molecules and and/or; (2) the loss of function of normal tau molecules in patients' brains. To test the l atter hypothesis, we performed behavioral and neurological tests on tau-def icient mice. Tau-deficient mice showed muscle weakness in the wire-hanging test, hyperactivity in a novel environment, and impairment in the contextua l fear conditioning. They also had a tendency to fall more easily in the ro d-walking test. These phenotypes parallel some signs and symptoms of FTDP-1 7 patients. Our results show that the loss of tau protein may itself lead t o some of the neurological characteristics observed in FTDP-17 patients. (C ) 2000 Elsevier Science Ireland Ltd. All rights reserved.