Apparent Behavioral Benefits of Tau Overexpression in P301L Tau Transgenic Mice

Transgenic mice expressing human tau containing the P301L tau mutation (JNPL3; tau mice) develop motor neuron loss, paralysis and death between 7 and 12 months. Surprisingly, at 5 and 7 months of age, tau transgenic mice were superior to other genotypes in the rotarod task, and had near perfect scores on the balance beam and coat hanger tests. One tau transgenic mouse was performing at a superior level in the rotarod one day prior to developing paralysis. Cognitive function was also normal in the tau mice evaluated in the radial arm water maze and the Y-maze tasks. We also crossed the tau transgenic mice with Tg2576 amyloid-beta protein precursor (A beta PP) transgenic mice. Although A beta PP mice were deficient in the radial arm maze task, A beta PP + tau mice were not impaired, implying a benefit of the tau transgene. Some mice were homozygous for the retinal degeneration mutation (rd/rd) and excluded from the genotype analysis. Only the water maze task discriminated the rd/rd mice from nontransgenic mice. In conclusion, it seems that the modest tau overexpression or the presence of mutant tau in the JNPL3 tau mice may provide some benefit with respect to motor and cognitive performance before the onset of paralysis.