title: Expression of the Alzheimer's Disease Mutations AβPP695sw and PSEN1M146I in Double-Transgenic Göttingen Minipigs.
abstract: Mutations in the amyloid-β protein precursor gene (AβPP), the presenilin 1 gene (PSEN1) or the presenilin 2 gene (PSEN2) that increase production of the AβPP-derived peptide Aβ42 cause early-onset Alzheimer's disease. Rodent models of the disease show that further increase in Aβ42 production and earlier brain pathology can be obtained by coexpressing AβPP and PSEN1 mutations. To generate such elevated Aβ42 level in a large animal model, we produced Göttingen minipigs carrying in their genome one copy of a human PSEN1 cDNA with the Met146Ile (PSEN1M146I) mutation and three copies of a human AβPP695 cDNA with the Lys670Asn/Met671Leu (AβPPsw) double-mutation. Both transgenes were expressed in fibroblasts and in the brain, and their respective proteins were processed normally. Immunohistochemical staining with Aβ42-specific antibodies detected intraneuronal accumulation of Aβ42 in brains from a 10- and an 18-month-old pig. Such accumulation may represent an early event in the pathogenesis of Alzheimer's disease.
authors.affiliation: Department of Biomedicine (East), Aarhus University, Aarhus C, Denmark.
authors.forename: Jannik E
authors.initials: JE
authors.lastname: Jakobsen
authors.affiliation: Department of Biomedicine (East), Aarhus University, Aarhus C, Denmark.
authors.forename: Marianne G
authors.initials: MG
authors.lastname: Johansen
authors.affiliation: Department of Large Animal Sciences/Reproduction, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Animal Science, Aarhus University, Tjele, Denmark.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Animal Science, Aarhus University, Tjele, Denmark.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Animal Science, Aarhus University, Tjele, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Callesen
authors.affiliation: Department of Pathology, Randers Hospital, Randers, Denmark.
authors.forename: Margarita
authors.initials: M
authors.lastname: Melnikova
authors.affiliation: Department of Biomedicine (East), Aarhus University, Aarhus C, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Habekost
authors.affiliation: Department of Biomedicine (East), Aarhus University, Aarhus C, Denmark.
authors.forename: Carmela
authors.initials: C
authors.lastname: Matrone
authors.affiliation: Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medicine Göttingen, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Bouter
authors.affiliation: Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medicine Göttingen, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bayer
authors.affiliation: Department of Biomedicine (East), Aarhus University, Aarhus C, Denmark.
authors.forename: Anders Lade
authors.initials: AL
authors.lastname: Nielsen
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors.forename: Monika
authors.initials: M
authors.lastname: Duthie
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Fraser
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.|Department of Pathology, Randers Hospital, Randers, Denmark.
authors.forename: Ida E
authors.initials: IE
authors.lastname: Holm
authors.affiliation: Department of Biomedicine (East), Aarhus University, Aarhus C, Denmark.
authors.forename: Arne Lund
authors.initials: AL
authors.lastname: Jørgensen
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics*; D013552:Swine; D013556:Swine, Miniature; D014162:Transfection
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer’s disease; amyloid; porcine model; presenilin; transgenic