Transgene: Human APP695 cDNA
Mutation: APP695 with double mutations
at KM670/671NL
Promoter: hamster prion protein gene promoter
Mouse Strain: C57B6j X SJL F1 hybrid mice backcrossed N1 or N2 generations
to C57B6j
Neuropathological analysis:
Brain transgenic APP was 5.6 times more than endogenous APP. A fivefold increase
in Ab(1-40) and a 14 fold increase in Ab(1-42/43)
over levels measure in young, unimpaired transgenic mice.
Numerous Ab plaques stained with Congo red dye in cortical
and limbic structures of mice with elevated amount of Ab.
Plaque load in these mice ranged from 3.6 to 8.5% in selected cellular inflammatory
response. Amyloid angiopathy appeared in some vessels. Markers to oxidative lipid
and glycoxidative damages as well as to the antioxidant defense enzymes heme-oxygenase
and superoxide dismutase were increased in transgenic animals.
Neither neuronal loss in the CA1 region nor loss of synaptic density in the dentate
gyrus of hippocampi in aged mice was detected.
Behavioral:
Normal spatial reference memory in N2 mice at 3 months. In a forced alternation
paradigm and spatial reference memory in a water maze were impaired in N2 mice at
14-16 months.
9-10 months N1 mice: spatial reference impairment.
Taconic Farm Emerging Model
TgN(APPSWE)2576 Model
#001349-T/W
Patent:
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5,877,399
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Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease
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Johns Hopkins University; Regents of the University of Minnesota /Hsiao; Karen;
Borchelt; David R.; Sisodia; Sangram S.
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6/17/96
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3/2/99
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Primary:
Hsiao, K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin
S, Yang F, Cole G. Correlative memory deficits, Ab
elevation, and amyloid plaques in transgenic mice. Science 274:99-102, Oct 4, 1996.
Abstract.
Associated:
Kawarabayashi T, Younkin L, Saido T, Shoji M, Ashe K, Younkin S. Age-dependent changes
in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse
model of Alzheimer's disease. J Neurosci 2001 Jan 15;21(2):372-81.
Abstract.
Frautschy SA, Yang F, Irrizarry M, Hyman B, Saido TC, Hsiao K, Cole GM. Microglial
response to amyloid plaques in APPsw transgenic mice. Am J Pathol 1998 Jan;152(1):307-17.
Abstract.
Irizarry MC, McNamara M, Fedorchak K, Hsiao K, Hyman BT. APPSw transgenic mice develop
age-related A beta deposits and neuropil abnormalities, but no neuronal loss in
CA1. J Neuropathol Exp Neurol 1997 Sep;56(9):965-73.
Abstract.
Lehman E J, Kulnane LS, Lamb BT. Alterations in b-amyloid
production and deposition in brain regions of two transgenic models. Neurobiol Aging
24 (5):645-653, 2003.
Abstract
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