Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice.
Tau, one of the major neuronal microtubule-associated proteins (MAPs), is important for neuronal cell morphogenesis and axonal maintenance. Tau is also known to be a component of the paired helical filaments (PHFs) in Alzheimer's disease patients. Recently, mutations in the tau gene were found in a hereditary neurodegenerative disease called frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) which exhibits various neurological 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 latter hypothesis, we performed behavioral and neurological tests on tau-deficient mice. Tau-deficient mice showed muscle weakness in the wire-hanging test, hyperactivity in a novel environment, and impairment in the contextual fear conditioning. They also had a tendency to fall more easily in the rod-walking test. These phenotypes parallel some signs and symptoms of FTDP-17 patients. Our results show that the loss of tau protein may itself lead to some of the neurological characteristics observed in FTDP-17 patients.
Ikegami
S
S
Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Harada
A
A
Hirokawa
N
N
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001921:Brain / Q000503:physiopathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003213:Conditioning, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D006801:Humans; D006948:Hyperkinesis / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018908:Muscle Weakness / Q000503:physiopathology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000503:physiopathology; D016875:tau Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
D016875:tau Proteins