General Information

Posted 30 October 2005

with Transgene: Combined transgenic mice overexpressing the enzyme GSK-3β (Tet/GSK3β), with transgenic mice expressing Tau with a triple FTDP-17 mutation which develop prefibrillar tau-aggregates (Tau^VLW miceM)(G272V, P301L and R406W)

Mutation: GSK3β/Tau (G272V, P301L and R406W)

Promoter: Thy1.2 promoter for Tau^vlwCamKIIα promoter for wtGSK-3β expression in Tet/GSK3β

Mouse Strain: C57Bl6jxCBA (Tau^vlw)

Phenotype

Neuropathological Analysis:

Co-expression of hTau^vlw and GSK-3β increased GSK-3β activity observed in hippocampus. Triple tg mice show tau hyperphosphorylation in hippocampal neurons, accompanied by thioflavin-S staining, and formation of filaments (> 10nm). The atrophy of the hippocampal dentate gyrus observed in Tet/GSK-3β mice develops much faster in Tet/GSK-3β/^vlw mice.

Availability

Contact: Felix Hernandez or Jesus Avila
Centro de Biología Molecular "Severo Ochoa," Facultad de Ciencias
Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain
Phone: +34-91-497-8440
Fax: +34-91-497-4799
Email: Jesus Avila or Felix Hernandez

Patent:
European Patent Application No 01936609.5. Model for neurodegenerative disease. JJ Lucas, F Hernandez, J Avila

References

Primary:

Engel T, Lucas JJ, Gomez-Ramos P, Moran MA, Avila J, Hernandez F. Co-expression of FTDP-17 tau and GSK-3beta in transgenic mice induce tau polymerization and neurodegeneration. Neurobiol Aging. 2005 Jul 26.

Associated:

Lucas J J, Hernandez F, Gomez-Ramos P, Moran M A, Hen R, Avila J. Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J. 2001 Jan 15;20(1-2):27-39. Abstract.

Lim F, Hernandez F, Lucas JJ, Gomez-Ramos P, Moran MA, Avila J. FTDP-17 mutations in tau transgenic mice provoke lysosomal abnormalities and Tau filaments in forebrain, Mol Cell Neurosci 18 (2001) (6), pp. 702-714. Abstract