Updated 9 July 2004
Transgene: Human longest brain tau isoform, wildtype 4 repeat tau isoform containing
exons 2 and 3 as well as four microtubule-binding repeats (2+ 3+ 4R human tau40)
Mutation: P301L (pR5 construct) Line: pR5-182
Promoter: Neuron-specific elements of the mouse Thy.1.2 promoter
Mouse strain: B6D2F1 x B6D2F1, founder animals were intercrossed with C57BL/6 mice
to establish lines.
Abnormal tau filament formation in P301L mice. Filaments were phosphorylated at
distinct epitopes, and formation accompanied by astrocytosis and apoptosis.
Tau filaments obtained from P301L mice have the same width as those in the human
disease associated with Dutch family 1 mutation, but shorter than filaments enriched
from AD brains.
Large numbers of pathologically enlarged axons containing neurofilament and
In cortex, brain stem, and spinal cord, neurofibrillary tangles were identified
by thioflavin-S fluorescent microscopy and Gallyas silver stains.
Injection of synthetic Ab42 fibrils into sensory cortex
and hippocampus of 5- to 6-month-old P301L mice leads to a 5-fold increase (relative
to uninjected Tg mice) in the number of neurofibrillary tangles found in amygdala
(from which neurons project to injection sites), along with smaller numbers in parietal
cortex. Injected wild-type mice did not show tangles.
Gallyas silver staining identified tangles containing tau phosphorylated at serine
212/threonine 214 and serine 422.
The neurofibrillary tangles were found as early as 18 days after injection and were
composed of twisted filaments.
Neuronal lesions similar to FTDP-17
Signs of Wallerian degeneration, neurogenic muscle atrophy, muscle weakness.
mice lacking exon 2 and 3 under the control of the mouse prion protein promoter
show an advanced neurological phenotype.
Gotz J, Chen F, Barmettler R, Nitsch RM. Tau filament formation in transgenic mice
expressing P301L tau. J Biol Chem 2001 Jan 5;276(1):529-34.
Gotz J, Chen F, van Dorpe J, Nitsch RM. Formation of neurofibrillary tangles in
P301l tau transgenic mice induced by Aβ42 fibrils. Science 293(5534):1491-5,
Gotz J, Barmettler R, Ferrari A, Goedert M, Probst A, Nitsch RM. In vivo analysis
of wild-type and FTDP-17 tau transgenic mice. Ann N Y Acad Sci 2000;920:126-33.
Pennanen L, Welzl H, D'Adamo P, Nitsch RM, Götz J. Accelerated extinction of conditioned
taste aversion in P301L tau transgenic mice. Neurobiol Dis. 2004 Apr ; 15(3):500-9.