Posted 26 July 2005
Transgene: Crossed APPV717I
(London) with PS1A246E
PS1A246E to produce bigenic mice.
Mutation: APP-V717I (London), PS1-A246E
Promoter: Mouse Thy1
Mouse strain: FVB/N
Bigenic mice co-express both transgenes in neurons only. Amyloidogeneic processing
of APP metabolism was increased in the brain of the bigenic mice. At 6-9 months
there were increased Aβ levels, concomittant with earlier and increased amyloid
plaques and vascular amyloid (CAA) compared to the single APP/London tg mice, which
develop plaques and CAA at 12-15 months.
Mutant PS1 aggravated parenchymal and cerebrovascular amyloid pathology (Van Dorpe,
2000) by increasing Aβ42 production, as opposed to aging in single APP-V717I
mice in which the increased amyloid pathology did not result from increased Aβ42
production, but from a decreased clearance (Dewachter et al, 2000). Increased Ca2+
release from the ER in mutant PS1 neurons was dependent on the presence of APP and
its processing by PS1 (i.e. amyloidβ and APP C99 fragments) (Herms et al, 2003).
Mice can be made available for academic collaboration under MTA with KULeuven-R&D.
For information on these mice, please contact:
Paul Van Dun
Director - KULeuvenR&D
Groot Begijnhof 59
B-3000 Leuven Belgium
tel +32 16 326508
fax +32 16 326515
Web site: http://www.kuleuven.ac.be/lrd
Dewachter I. Aging increased amyloid peptide and caused amyloid plaques in brain
of old APP/V717I transgenic mice by a different mechanism than mutant presenilin1.
J Neurosci. 2000 Sep 1;20(17):6452-8. Abstract
Dewachter I, Reversé D, Caluwaerts N, Ris L, Kuipéri C, Van den Haute C, Spittaels
K, Umans L, Serneels L, Thiry E, Moechars D, Mercken M, Godaux E, Van Leuven F.
Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and corrects
hippocampal long-term potentiation but not a cognitive defect of amyloid precursor
protein [V717I] transgenic mice. J Neurosci. 2002 May 1 ; 22(9):3445-53.
Van Dorpe J, Smeijers L, Dewachter I, Nuyens D, Spittaels K, Van Den Haute C, Mercken
M, Moechars D, Laenen I, Kuiperi C, Bruynseels K, Tesseur I, Loos R, Vanderstichele
H, Checler F, Sciot R, Van Leuven F. Prominent cerebral Amyloid Angioplathy in APP/London
transgenic mice. Am J Pathol (2000) 157:1283-1298.
Schneider I, Reverse D, Dewachter I, Ris L, Caluwaerts N, Kuiperi C, Gilis M, Geerts
H, Kretzschmar H, Godaux E, Moechars D, Van Leuven F, Herms J. Mutant presenilins
disturb neuronal calcium homeostasis in the brain of transgenic mice, decreasing
the threshold for excitotoxicity and facilitating long-term potentiation. J Biol
Chem. 2001 Apr 13; 276(15): 11539-44.
Herms J, Schneider I, Dewachter I, Caluwaerts N, Kretzschmar H, Van Leuven F. Capacitive
calcium entry is directly attenuated by mutant presenilin-1, independent of the
expression of the amyloid precursor protein. J Biol Chem. (2003) 278: 2484-2489.
Moechars D. Early phenotypic changes in transgenic mice that overexpress different
mutants of amyloid precursor protein in brain. J Biol Chem. 1999 Mar 5;274(10):6483-92.