Posted 10 June 2005

General Information

Transgene: The tau knock-out/knock-in strain of human wild-type tau-4R/2N (tau-KOKI) aimed to inactivate the endogenous murine tau gene and to replace it with a single copy of the thy1-tau-4R/2N recombinant DNA construct. This construct was linearized and ligated in a unique NcoI site in exon 1 of the mouse tau gene. A 1.9-kb NotI fragment encoding the marker gene hygromycin B phosphotransferase driven by the phosphoglycerate kinase gene promoter was further ligated into a unique SmaI site. The targeting vector was linearized by NotI restriction and purified before electroporation into ES. Desired ES cell colonies were microinjection into 4-day-old blastocysts from pregnant C57Bl/6 female mice. Reimplantation into pseudopregnant CD1 females by uterine transfer resulted in brown coat color chimeric mice proving germ line transmission of the ES cells. Offspring from the chimeras were back-crossed with FVB/N mice for 8 generations and to reach homozygosity for the recombinated tau-locus .

Mutation: hTau 4R/2N, no mouse endogenous Tau

Promoter: Thy1

Mouse strain: FVB/N Backcross N8

Phenotype

Neuropathological Analysis:

Expression level, similar to endogenous mouse tau with all isoforms combined.Axonal dilations, absent. Tau aggregates, absent.

Behavioral:

Rotarod, slight impairment > 6 months Clasping, normal. Beam, slight impairment > 6 months. Mean life span: normal

Availability

Licensing/academic distribution contact information:

Paul Van Dun
Director - KULeuvenR&D
Groot Begijnhof 59
B-3000 Leuven Belgium
tel +32 16 326508
fax +32 16 326515
Email: Paul.Vandun@lrd.kuleuven.ac.be
Web site: http://www.kuleuven.ac.be/lrd

Patents: none

References

Primary:

Terwel D, Lasrado R, Snauwaert J, Vandeweert E, Van Haesendonck C, Borghgraef P, Van Leuven F.Changed conformation of mutant tau-P301L underlies the moribund tauopathy, absent in progressive, non-lethal axonopathy of tau-4R/2N transgenic mice. J Biol Chem (2005) 280: 3963-3973. Abstract.