Sci. Aging Knowl. Environ., 27 October 2004
Vol. 2004, Issue 43, p. tg5
[DOI: 10.1126/sageke.2004.43.tg5]

GENETICALLY ALTERED MICE

Amyloid Precursor Protein (APP) E693Q Transgenic Mice (APPDutch Mice)

http://sageke.sciencemag.org/cgi/content/full/2004/43/tg5


Mouse APPDutch mice; human APP E693Q transgenic mice
Genetic background C57BL/6J
Gene changed The human APP751 cDNA encoding a Glu693->Gln693 (E693Q) mutation (affecting residue 22 in amyloid-beta protein) was inserted into a vector containing the murine Thy1.2 minigene. The neuron-specific Thy1 promoter element controls the expression of the human transgene in this construct. Linear Thy1-APP constructs were injected into oocytes.
Type of change The expression level of the mutant human amyloid precursor protein (APP) is approximately five times greater than that of the endogenous APP.
Nature of protein The E693Q point mutation in APP affects residue 22 of amyloid-beta.
Phenotype In mice, overexpression of human APP containing the E693Q point mutation causes extensive cerebral amyloid angiopathy, degeneration of smooth muscle cells, neuroinflammation, and hemorrhage.
Corresponding human phenotype The E693Q point mutation results in hereditary cerebral hemorrhage with amyloidosis characterized by recurrent lobar cerebral hemorrhages beginning in the fifth decade of life. Amyloid plaques are not prominent; instead, diffuse parenchymal amyloid-beta is observed.
Primary reference M. C. Herzig, D. T. Winkler, P. Burgermeister, M. Pfeifer, E. Kohler, S. D. Schmidt, S. Danner, D. Abramowski, C. Sturchler-Pierrat, K. Burki, et al., Amyloid-beta is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis. Nat. Neurosci. 7, 954-960 (2004).
Additional references See below.
Source Contact the author of the primary reference, Mathias Jucker (mathias.jucker{at}uni-tuebingen.de).
Other comments Transgenic mice with the E693Q mutation predominantly produce amyloid-beta 40, which accumulates vascularly. The authors suggest that therapeutic approaches for treating Alzheimer's disease that increase the ratio of amyloid-beta 40 to amyloid-beta 42 may have an unwanted side effect: the promotion of cerebral amyloidosis.
Other links Related transgenic mice:
APP/Ld (Van Dorpe et al. 2000)
APP23 (Winkler et al. 2001)
Tg2576 (Christie et al. 2001)
SAGE KE's Genes/Interventions database:
APP
Keywords cerebral amyloidosis
amyloid-beta
hemorrhage
neuroinflammation
Prepared by Galynn Zitnik


October 27, 2004
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Citation: Amyloid Precursor Protein (APP) E693Q Transgenic Mice (APPDutch Mice). Sci. Aging Knowl. Environ. 2004 (43), tg5 (2004).








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