Posted 30 October 2005
Transgene: Crossed APPSwe
(Tg2576) and Tauvlw
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)
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-tauvlw female mice in comparison to male mice. Co-expression of
human mutant APP and tau in the APPsw-tauvlw 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-tauvlw
and APPsw brains, and significant neuronal loss in the EC in the former. By 16 months,
however, both APPsw and APPsw-tauvlw mice showed marked spatial reference
memory impairment compared to tauvlw and non-transgenic littermate controls.
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.
European Patent Application No 01936609.5. Model for neurodegenerative disease.
JJ Lucas, F Hernandez, J Avila
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.
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.