Transgene: APP RK cDNA
Mutation: a-secretion is reduced by the substitution
of two basic with two acidic residues in the a-secretase
cleavage site. Lysine 687 replaced with glutamic acid, Arginine 684 replaced
with aspartic acid. (K687E, R684D).
Promoter: mouse Thy-1 gene promoter
Mouse Strain: FVB/N
Neuropathological Analysis
APP/RK Tg mice exhibited stronger immunoreactivity in neurons of the cortex, amygdala
and striatum, but also in the granular layer of the dentate gyrus, which hardly
contains APP in the wt mice.
APP/RK Tg displayed extensive apoptosis in hippocampus and cortex, also displayed
an aberrant staining pattern for synaptophysin due to loss of neurites.
No differences observed in Timm stain between wt and APP/RK mice.
Behavioral
Homozygous APP/RK Tg exhibited posture freezing when exposed to a new environment
as early as 12 weeks. The corner corssing scores of the Tg mice age 17-30
week was significantly lower compared to that the non-transgenic.
In Open Field test, Tg mice exhibited a reduced locomotor activity during the first
5 minutes.
APP/RK mouse exhibits premature death, increased aggression, decreased locomotor
activity, increased spontaneous seizures, age dependency of neophobic reaction,
functional disturbance and hypo-sensitivity to glutamate receptor agonists (NMDA),
but none of the typical neuropathological hallmarks of AD such as amyloid deposition
and tau pathology are detected in the brain
Licensing/academic distribution contact information:
Paul Van Dun
Director - KULeuvenR&D
Groot Begijnhof 59
B-3000 Leuven Belgium
tel +32 16 326508
fax +32 16 326515
Email: Paul.Vandun@lrd.kuleuven.ac.be
Web site: http://www.kuleuven.ac.be/lrd
Patents: None
Primary:
Moechars D, Lorent K, De Strooper B, Dewachter I, Van Leuven F. Expression in brain
of amyloid precursor protein mutated in the alpha-secretase site causes disturbed
behavior, neuronal degeneration and premature death in transgenic mice. EMBO J 1996
Mar 15;15(6):1265-74.
Abstract.
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