Posted 3 March 2005
Transgene: Human tau minigene that overexpresses three human brain tau isoforms
with 3RT was created in pKS vector by embedding a modified genomic version of tau
exons 1 to 4 (containing introns that flank exons 2 and 3) in a cDNA for the shortest
tau isoform (exons -1 to 13 without exons 4A, 6, 8, and 10). The tubulin Tα1
promoter was cloned into pcDNA3 vector, and the XmnI site on pcDNA3 was modified
to an AscI site. Transgenic construct (Tα1-3RT) was made by ligating a SalI/PvuII
fragment of the minigene construct into a KpnI/NotI-fragment of the Tα-1 promoter
vector. The Tα1-3RT was cut, purified, microinjected into fertilized B6SJL/F1
mouse eggs, and reimplanted into pseudopregnant females. Line 14 with the highest
transgene copy number and highest tau protein expression was propagated and used.
Promoter: Mouse tubulin Tα1 promoter
Mutation: Tau 3 human RT
Mouse strain: B6SJL, maintained as heterozygous
Generated a tau Tg mouse model of FTD that developed glial tau pathologies. Progressive
accumulations of tau in astrocytes and oligodendrocytes were closely associated
with degeneration of these cells as well as with disruption of myelin sheaths. Aged
Tg mice showed numerous glial tau inclusions that were morphologically, histochemically,
and immunohistochemically similar to the glial tau pathologies in FTDs, such as
PSP, PiD, PSG, CBD, and FTDP-17.
Mice developed progressive motor weakness, including impaired ability to stand on
a slanted surface and dystonic movement of the hindlimbs or both hindlimbs and forelimbs
when lifted by their tails. By 24 months of age, limb twitch was observed in 72%
of Tg mice, compared with 18% of WT mice.
Virginia M. -Y. Lee
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory
University of Pennsylvania School of Medicine
Philadelphia, PA 19104 USA
Higuchi M, Ishihara T, Zhang B, Ming Hong M, Andreadis A, Trojanowski J Q, and Lee
V M-Y. Transgenic Mouse Model of Tauopathies with Glial Pathology and Nervous System
Degeneration. Neuron 35:433-446, 2002.
Macknin J B, Higuchi M, Lee V M-Y, Trojanowski J Q and Doty R L. Olfactory dysfunction
occurs in transgenic mice overexpressing human t protein. Brain Res. 1000:174-178,