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Regulatory region of human amyloid precursor protein (APP) gene promotes neuron‐specific gene expression in the CNS of transgenic mice.
Author(s) -
Wirak D. O.,
Bayney R.,
Kundel C. A.,
Lee A.,
Scangos G. A.,
Trapp B. D.,
Unterbeck A. J.
Publication year - 1991
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1991.tb07949.x
Subject(s) - biology , transgene , amyloid precursor protein , gene , genetically modified mouse , gene expression , microbiology and biotechnology , genetics , alzheimer's disease , disease , medicine , pathology
The accumulation of beta‐amyloid protein in specific brain regions is a central pathological feature of Alzheimer's disease (AD). The 4 kd beta‐amyloid protein derives from a larger amyloid precursor protein (APP) by as yet unknown mechanisms. In the absence of a laboratory animal model of AD, transgenic mice expressing various APP gene products may provide new insights into the relationship between APP and beta‐amyloid formation and the pathogenesis of AD. beta‐amyloid accumulation in AD brain may result from interactions between APP and other molecules. Such interactions are likely to be developmentally regulated and tissue‐specific. A transgenic mouse model of AD, therefore, would aim for APP transgene expression that mimics the endogenous APP gene. As an initial step in developing an animal model, we have identified a 4.5 kb DNA fragment from the 5′ end of the human APP gene, which mediates neuron‐specific gene expression in the CNS of transgenic mice, using E. coli lacZ as a reporter gene. Detectable levels of transgene expression are found in most neurons but not in glial and vascular endothelial cells. The expression pattern of this reporter gene closely resembles the distribution of endogenous APP mRNA in both the human and mouse CNS.