Sci. Aging Knowl. Environ., 4 February 2004
Vol. 2004, Issue 5, p. tg1
[DOI: 10.1126/sageke.2004.5.tg1]


Amyloid Precursor Protein (APP) Transgenic Mice (Tg2576 Mice)

Mouse Amyloid precursor protein (APP) transgenic mice (Tg2576 mice).
Genetic background Tg(HuAPP695 SWE)2576 was originally generated in a hybrid C57Bl/6J x SJL background. The transgenic mice were backcrossed to C57Bl/6J for two generations and then crossed to C57Bl/6J x SJL F1 hybrid.
Gene changed The gene encoding the 695-amino acid isoform of a mutant form of human amyloid precursor protein (APP) was inserted into mice using a hamster prion protein cosmid vector, in which APP replaced the prion protein open reading frame. Expression of APP is driven by the hamster prion protein gene promoter.
Type of change In this strain, an Alzheimer's disease (AD)-associated mutant variant of human APP (Lys670->Asn670, Met671->Leu671) is overexpressed. The variant was found in a Swedish family with early-onset AD.
Nature of protein APP is a large membrane-spanning protein that is cut by proteases into several smaller peptides, including the beta-amyloid peptide found in neuritic plaques in AD patients.
Phenotype These mice express high levels of mutant beta-amyloid and, with increasing age, develop both substantial amyloid plaque load and memory deficits.
Corresponding human phenotype In Alzheimer's disease, amyloid plaques accumulate in the cerebral cortex, hippocampus, and amygdala and correlate with memory deficits.
Primary reference K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, G. Cole, Correlative memory deficits, beta-amyloid elevation, and amyloid plaques in transgenic mice. Science 274, 99-102 (1996).
Additional references See below.
Source Tg2576 mice are commercially available from Taconic Animal Models, Germantown, NY, USA ( This is the APP microinjected mouse model [B6;SJL-Tg(APPSWE)2576Kha]. Order model no.: 001349-T (hemizygous); 001349-W (nontransgenic control).
Other comments With increasing age, Tg2576 mice also exhibit increased lipid peroxidation in brain tissues. Sung et al. (2003) fed 8 to 10 international units of vitamin E per day to two groups of Tg2576 mice. In the first group, feeding started at 5 months of age and continued to 13 months of age; and in the second group, feeding started at 14 months of age and continued to 20 months of age. Mice fed vitamin E at young ages exhibited less lipid peroxidation, lower amounts of beta-amyloid, and less plaque formation relative to placebo-fed mice. Mice fed vitamin E at older ages exhibited less lipid peroxidation but did not display significantly different amounts of beta-amyloid or plaque formation as compared to control mice. The authors suggest that oxidative stress might play a causal role in the amyloid cascade, a role that must be suppressed early in life to prevent plaque deposition and associated damage.
Other links Related transgenic mice:
Mice that are transgenic for both HuAPP695 SWE and human variants of presenilin 1 (A246E or DeltaE9) exhibit even more extreme AD-like pathology than Tg2576 mice.
See also:
Triple-Transgenic Alzheimer's Disease Model Mice
SAGE KE's Genes/Interventions database:
Keywords amyloid-beta plaques
neurofibrillary tangles
Alzheimer's disease
amyloid cascade hypothesis
lipid peroxidation
vitamin E
Prepared by Galynn Zitnik

February 4, 2004
  1. P. F. Chapman, G. L. White, M. W. Jones, D. Cooper-Blacketer, V. J. Marshall, M. Irizarry, L. Younkin, M. A. Good, T. V. P. Bliss, B. T. Hyman, et al., Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat. Neurosci. 2, 271-276 (1999).[CrossRef][Medline]
  2. K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, G. Cole, Correlative memory deficits, beta-amyloid elevation, and amyloid plaques in transgenic mice. Science 274, 99-102 (1996).[Abstract/Free Full Text]
  3. D. Praticó, K. Uryu, S. Leight, J. Q. Trojanowski, V. M.-Y. Lee, Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J. Neurosci. 21, 4183-4187 (2001).[Abstract/Free Full Text]
  4. S. Sung, Y. Yao, K. Uryu, H. Yang, V. M.-Y. Lee, J. Q. Trojanowski, D. Praticó, Early vitamin E supplementation in young but not aged mice reduces beta-amyloid levels and amyloid deposition in a transgenic model of Alzheimer's disease. FASEB J., 4 December 2003 [e-pub ahead of print]. [Abstract].
Citation: Amyloid Precursor Protein (APP) Transgenic Mice (Tg2576 Mice). Sci. Aging Knowl. Environ. 2004 (5), tg1 (2004).

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