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Lookup NU author(s): Professor Colin Dingwall
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BACE1 is a key enzyme in the generation of Abeta, the major component of senile plaques in the brains of Alzheimer's disease patients. We have generated transgenic mice expressing human BACE1 with the Cam Kinase II promoter driving neuronal-specific expression. The transgene contains the full-length coding sequence of human BACE1 preceding an internal ribosome entry site element followed by a LacZ reporter gene. These animals exhibit a bold, exploratory behavior and show elevated 5-hydroxytryptamine turnover. We have also generated a knockout mouse in which LacZ replaces the first exon of murine BACE1. Interestingly these animals show a contrasting behavior, being timid and less exploratory. Despite these clear differences both mouse lines are viable and fertile with no changes in morbidity. These results suggest an unexpected role for BACE1 in neurotransmission, perhaps through changes in amyloid precursor protein processing and Abeta levels.
Author(s): Dingwall C; Harrison SM; Harper AJ; Hawkins J; Duddy G; Grau E; Pugh PL; Winter PH; Shilliam CS; Hughes ZA; Dawson LA; Gonzalez MI; Upton N; Pangalos MN
Publication type: Article
Publication status: Published
Journal: Molecular and Cellular Neuroscience
Year: 2003
Volume: 24
Issue: 3
Pages: 646-655
ISSN (print): 1044-7431
ISSN (electronic): 1095-9327
Publisher: Academic Press
URL: http://dx.doi.org/10.1016/S1044-7431(03)00227-6
DOI: 10.1016/S1044-7431(03)00227-6
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