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:
| 5,877,399 |
Transgenic mice expressing APP-Swedish
mutation develop progressive neurologic disease |
Johns Hopkins University; Regents
of the University of Minnesota /Hsiao; Karen; Borchelt;
David R.; Sisodia; Sangram S. |
6/17/96 |
3/2/99 |
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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