title: Mutant presenilin 2 transgenic mouse: effect on an age-dependent increase of amyloid beta-protein 42 in the brain.
abstract: The N141I missense mutation in presenilin (PS) 2 is tightly linked with a form of autosomal dominant familial Alzheimer's disease (AD) in the Volga German families. We have generated transgenic mouse lines overexpressing human wild-type or mutant PS2 under transcriptional control of the chicken beta-actin promoter. In the brains of transgenic mice, the levels of human PS2 mRNA were found to be five- to 15-fold higher than that of endogenous mouse PS2 mRNA. The amyloid beta-protein (Abeta) 42 levels in the brains of mutant PS2 transgenic mice were higher than those in wild-type PS2 transgenic mice at the age of 2, 5, or 8 months. In addition, the Abeta42 levels appeared to increase steadily in the mutant PS2 transgenic mouse brains from 2 to 8 months of age, whereas there was only a small increase in wild-type transgenic mice between the ages of 5 and 8 months. There was no definite difference in the levels of N-terminal and C-terminal fragments between wild-type and mutant PS2 transgenic mice at the age of 2, 5, or 8 months. These data show a definite effect of the PS2 mutation on an age-dependent increase of Abeta42 content in the brain.
authors.affiliation: Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Oyama
authors.forename: N
authors.initials: N
authors.lastname: Sawamura
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Morishima-Kawashima
authors.forename: T
authors.initials: T
authors.lastname: Kuramochi
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: T C
authors.initials: TC
authors.lastname: Saido
authors.forename: T
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: A
authors.initials: A
authors.lastname: Capell
authors.forename: J
authors.initials: J
authors.lastname: Walter
authors.forename: J
authors.initials: J
authors.lastname: Grünberg
authors.forename: Y
authors.initials: Y
authors.lastname: Ueyama
authors.forename: C
authors.initials: C
authors.lastname: Haass
authors.forename: Y
authors.initials: Y
authors.lastname: Ihara
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D002458:Cell Fractionation; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism*; D053766:Presenilin-2; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D053766:Presenilin-2; D012333:RNA, Messenger; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)