Mutant presenilin 2 transgenic mouse: effect on an age-dependent increase of amyloid beta-protein 42 in the brain.
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.
Oyama
F
F
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
Sawamura
N
N
Kobayashi
K
K
Morishima-Kawashima
M
M
Kuramochi
T
T
Ito
M
M
Tomita
T
T
Maruyama
K
K
Saido
T C
TC
Iwatsubo
T
T
Capell
A
A
Walter
J
J
Grünberg
J
J
Ueyama
Y
Y
Haass
C
C
Ihara
Y
Y
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
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)