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

Neurosci Lett. 2000 Feb 4;279(3):129-32. doi: 10.1016/s0304-3940(99)00964-7.


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.

MeSH terms

  • Animals
  • Avoidance Learning / physiology
  • Brain / physiopathology
  • Chromosomes, Human, Pair 17 / genetics
  • Conditioning, Psychological / physiology*
  • Fear / physiology*
  • Humans
  • Hyperkinesis / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Weakness / physiopathology*
  • Neurodegenerative Diseases / physiopathology
  • Parkinsonian Disorders / physiopathology
  • tau Proteins / deficiency*
  • tau Proteins / genetics*
  • tau Proteins / metabolism


  • tau Proteins