BACE1 (beta-secretase) transgenic and knockout mice: identification of neurochemical deficits and behavioral changes
| Autor: | Panida Winter, Neil Upton, Alex J. Harper, Lee A. Dawson, Steve Mark Harrison, Julie Hawkins, M. Isabel Gonzalez, Pippa L Pugh, Menelas N. Pangalos, Zoe A. Hughes, Claire S. Shilliam, Evelyn Grau, Colin Dingwall, Graham Duddy |
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| Rok vydání: | 2003 |
| Předmět: |
Genetically modified mouse
Serotonin Transgene BACE1-AS Mice Transgenic Synaptic Transmission Cellular and Molecular Neuroscience Mice Alzheimer Disease Genes Reporter Ca2+/calmodulin-dependent protein kinase mental disorders Endopeptidases Amyloid precursor protein Animals Aspartic Acid Endopeptidases Senile plaques Transgenes Molecular Biology Cells Cultured Mice Knockout Amyloid beta-Peptides biology Behavior Animal Brain Cell Biology Fear Molecular biology Disease Models Animal Phenotype Knockout mouse biology.protein Exploratory Behavior Amyloid Precursor Protein Secretases Amyloid precursor protein secretase |
| Zdroj: | Molecular and cellular neurosciences. 24(3) |
| ISSN: | 1044-7431 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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