Updated 25 January 2006

General Information

Transgene: The three FTDP-17 linked mutations G272V (V), P301L (L) and R406W (W) were incorporated by site-directed mutagenesis of human CNS tau cDNA (2 N-terminal inserts, 4 microtubule-binding repeats) then inserted into a murine Thy1 cassette between exons 2 and 4.

Mutation: FTDP-17; G272V, P301L and R406W

Promoter: Mouse Thy-1 promoter with deleted lymphoid enhancer

Mouse Strain: C57Bl6j

Phenotype

Neuropathological Analysis:

Tau^vlw mice overexpress human mutant Tau in cortex and hippocampus with minimal expression in the spinal cord. Immunohistochemical analysis reveals high transgene expression in neuronal cell bodies and neurites in the cortex and the hippocampal formation. Ultrastructural analysis shows a pretangle appearance in neurons expressing mutant tau, with filaments of tau and increased numbers of lysosomes displaying aberrant morphology similar to those found in AD

Behavioral:

Availability

J. 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: javila@cbm.uam.es

Patents:

References

Primary:

Lim, F., Hernández F., Lucas J.J., Gómez-Ramos P., Morán M.A. and Ávila J. FTDP-17 mutations in tau transgenic mice provoke lysosomal abnormalities and Tau filaments in forebrain. Mol. Cell. Neurosci. 18: 702-4, 2001. Abstract.

Associated:

Ferrer I, Barrachina M, Puig B, Martinez de Lagran M, Marti E, Avila J, Dierssen M. Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis. 2005 Nov;20(2):392-400. Abstract

Perez M, Hernandez F, Lim F, Diaz-Nido J, Avila J. Chronic lithium treatment decreases mutant tau protein aggregation in a transgenic mouse model. J Alzheimers Dis. 2003 Aug;5(4):301-8. Abstract