General Information

Posted 30 October 2005

Transgene: Crossed APPSwe (Tg2576) and Tau^vlw lines expressing human APP harboring the double Swedish mutation (APPswe) and human 4-repeat tau containing a triple mutation (G272V, P301L and R406W)

Mutation: App Swe, Tau (G272V, P301L and R406W)

Promoter: hamster prion protein gene promoter

Mouse Strain: C57Bl6jxSJL (APPSwe); C57Bl6jxCBA (Tauvlw)

Phenotype

Neuropathological Analysis:

Double transgenic mice showed enhanced amyloid deposition accompanied by neurofibrillary degeneration and overt neuronal loss in selectively vulnerable brain limbic areas. Not only resulted in increased tau phosphorylation but also triggered NFT-like formation in the EC and CA1 regions at 25 months of age. Fivefold higher amyloid burdens in APPsw-tau^vlw female mice in comparison to male mice. Co-expression of human mutant APP and tau in the APPsw-tau^vlw mouse model enhanced both A͎ and tau pathology and resulted in significant neuronal loss in selective vulnerable brain areas.

Behavior and age of phenotype:

Learning and memory deficits, as measured by the Morris watermaze test, were quite modest at 9 months of age despite incipient amyloid deposits in APPsw-tau^vlw and APPsw brains, and significant neuronal loss in the EC in the former. By 16 months, however, both APPsw and APPsw-tau^vlw mice showed marked spatial reference memory impairment compared to tauvlw and non-transgenic littermate controls.

Availability

Contact: Teresa Gómez-Isla or J. Avila
Departmento de Neurología
Hospital Santa Creu i Sant Pau
C/Sant Antoni Ma Claret, 167
Barcelona 08025, Spain.

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

References

Primary:

M. Perez, E. Ribe, A. Rubio, F. Lim, M.A. Moran, P.G. Ramos, I. Ferrer, M.T. Isla and J. Avila, Characterization of a double (amyloid precursor protein-tau) transgenic: tau phosphorylation and aggregation. Neuroscience 130 (2005), pp. 339-347. Abstract.

Associated:

Ribé EM, Pérez M, Puig B, Gich I, Lim F, Cuadrado M, Sesma T, Catena S, Sánchez B, Nieto M, Gómez-Ramos P, Morán MA, Cabodevilla F, Samaranch L, Ortiz L, Pérez A, Ferrer I, Avila J, Gómez-Isla T. Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice. Neurobiol Dis. 2005 Aug 23. 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. 2001 Dec;18(6):702-14. Abstract.