Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2

Authors

  • G. Azkona,

    1. Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), and
    2. CIBER de Enfermedades Raras (CIBERER), E-08003 Barcelona, Catalonia, Spain
    3. Department of Neuroscience, University of Basque Country (UPV/EHU), E-48003, Bizkaia, Spain
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  • A. Amador-Arjona,

    1. Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), and
    2. CIBER de Enfermedades Raras (CIBERER), E-08003 Barcelona, Catalonia, Spain
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  • C. Obradors-Tarragó,

    1. Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), and
    2. CIBER de Enfermedades Raras (CIBERER), E-08003 Barcelona, Catalonia, Spain
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  • E. Varea,

    1. Departments of Histology and Anatomy, University Miguel Hernández, Elche, E-03550, Alicante, Spain
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  • G. Arqué,

    1. Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), and
    2. CIBER de Enfermedades Raras (CIBERER), E-08003 Barcelona, Catalonia, Spain
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  • R. Pinacho,

    1. Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), and
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  • C. Fillat,

    1. Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), and
    2. CIBER de Enfermedades Raras (CIBERER), E-08003 Barcelona, Catalonia, Spain
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  • S. De La Luna,

    1. Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), and
    2. CIBER de Enfermedades Raras (CIBERER), E-08003 Barcelona, Catalonia, Spain
    3. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain
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  • X. Estivill,

    1. Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), and
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  • M. Dierssen

    Corresponding author
    1. Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), and
    2. CIBER de Enfermedades Raras (CIBERER), E-08003 Barcelona, Catalonia, Spain
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* M. Dierssen, Neurobehavioural Phenotyping of Mouse Models of Disease, Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), Dr. Aiguader, 88, 08003 Barcelona (Spain). E-mail: mara.dierssen@crg.es

Abstract

BACE2 is homologous to BACE1, a β-secretase that is involved in the amyloidogenic pathway of amyloid precursor protein (APP), and maps to the Down syndrome critical region of chromosome 21. Alzheimer disease neuropathology is common in Down syndrome patients at relatively early ages, and it has thus been speculated that BACE2 co-overexpression with APP would promote the early neurodegenerative phenotype. However, the in vivo function of BACE2 has not yet been elucidated. The aim of the present work has been to analyse the impact of in vivo BACE2 overexpression using a transgenic mouse model. Our results suggest that BACE2 is not involved in the amyloidogenic pathway, cognitive dysfunction or cholinergic degeneration. However, TgBACE2 animals showed increased anxiety-like behaviour along with increased numbers of noradrenergic neurones in locus coeruleus, thus suggesting an unexpected role of BACE2 overexpression.

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