Mutant presenilin 2 transgenic mouse: Effect on an age-dependent increase of amyloid β-protein 42 in the brain

Fumitaka Oyama, Naoya Sawamura, Kimio Kobayashi, Maho Morishima-Kawashima, Takashi Kuramochi, Mamoru Ito, Taisuke Tomita, Kei Maruyama, Takaomi C. Saido, Takeshi Iwatsubo, Anja Capell, Jochen Walter, Jürgen Grünberg, Yoshito Ueyama, Christian Haass, Yasuo Ihara

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

The N1411 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 β-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 β-protein (Aβ) 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 Aβ42 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 Aβ42 content in the brain.

Original languageEnglish
Pages (from-to)313-322
Number of pages10
JournalJournal of Neurochemistry
Volume71
Issue number1
Publication statusPublished - 1998 Jul
Externally publishedYes

Fingerprint

Presenilin-2
Amyloidogenic Proteins
Transgenic Mice
Brain
Serum Amyloid A Protein
Messenger RNA
Actins
Missense Mutation
Chickens
Alzheimer Disease
Mutation

Keywords

  • Alzheimer's disease
  • Amyloid β-protein
  • Presenilin 2
  • Transgenic mouse

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Oyama, F., Sawamura, N., Kobayashi, K., Morishima-Kawashima, M., Kuramochi, T., Ito, M., ... Ihara, Y. (1998). Mutant presenilin 2 transgenic mouse: Effect on an age-dependent increase of amyloid β-protein 42 in the brain. Journal of Neurochemistry, 71(1), 313-322.

Mutant presenilin 2 transgenic mouse : Effect on an age-dependent increase of amyloid β-protein 42 in the brain. / Oyama, Fumitaka; Sawamura, Naoya; Kobayashi, Kimio; Morishima-Kawashima, Maho; Kuramochi, Takashi; Ito, Mamoru; Tomita, Taisuke; Maruyama, Kei; Saido, Takaomi C.; Iwatsubo, Takeshi; Capell, Anja; Walter, Jochen; Grünberg, Jürgen; Ueyama, Yoshito; Haass, Christian; Ihara, Yasuo.

In: Journal of Neurochemistry, Vol. 71, No. 1, 07.1998, p. 313-322.

Research output: Contribution to journalArticle

Oyama, F, Sawamura, N, Kobayashi, K, Morishima-Kawashima, M, Kuramochi, T, Ito, M, Tomita, T, Maruyama, K, Saido, TC, Iwatsubo, T, Capell, A, Walter, J, Grünberg, J, Ueyama, Y, Haass, C & Ihara, Y 1998, 'Mutant presenilin 2 transgenic mouse: Effect on an age-dependent increase of amyloid β-protein 42 in the brain', Journal of Neurochemistry, vol. 71, no. 1, pp. 313-322.
Oyama, Fumitaka ; Sawamura, Naoya ; Kobayashi, Kimio ; Morishima-Kawashima, Maho ; Kuramochi, Takashi ; Ito, Mamoru ; Tomita, Taisuke ; Maruyama, Kei ; Saido, Takaomi C. ; Iwatsubo, Takeshi ; Capell, Anja ; Walter, Jochen ; Grünberg, Jürgen ; Ueyama, Yoshito ; Haass, Christian ; Ihara, Yasuo. / Mutant presenilin 2 transgenic mouse : Effect on an age-dependent increase of amyloid β-protein 42 in the brain. In: Journal of Neurochemistry. 1998 ; Vol. 71, No. 1. pp. 313-322.
@article{3efee3809d084b50aa827b3c27c3db61,
title = "Mutant presenilin 2 transgenic mouse: Effect on an age-dependent increase of amyloid β-protein 42 in the brain",
abstract = "The N1411 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 β-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 β-protein (Aβ) 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 Aβ42 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 Aβ42 content in the brain.",
keywords = "Alzheimer's disease, Amyloid β-protein, Presenilin 2, Transgenic mouse",
author = "Fumitaka Oyama and Naoya Sawamura and Kimio Kobayashi and Maho Morishima-Kawashima and Takashi Kuramochi and Mamoru Ito and Taisuke Tomita and Kei Maruyama and Saido, {Takaomi C.} and Takeshi Iwatsubo and Anja Capell and Jochen Walter and J{\"u}rgen Gr{\"u}nberg and Yoshito Ueyama and Christian Haass and Yasuo Ihara",
year = "1998",
month = "7",
language = "English",
volume = "71",
pages = "313--322",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Mutant presenilin 2 transgenic mouse

T2 - Effect on an age-dependent increase of amyloid β-protein 42 in the brain

AU - Oyama, Fumitaka

AU - Sawamura, Naoya

AU - Kobayashi, Kimio

AU - Morishima-Kawashima, Maho

AU - Kuramochi, Takashi

AU - Ito, Mamoru

AU - Tomita, Taisuke

AU - Maruyama, Kei

AU - Saido, Takaomi C.

AU - Iwatsubo, Takeshi

AU - Capell, Anja

AU - Walter, Jochen

AU - Grünberg, Jürgen

AU - Ueyama, Yoshito

AU - Haass, Christian

AU - Ihara, Yasuo

PY - 1998/7

Y1 - 1998/7

N2 - The N1411 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 β-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 β-protein (Aβ) 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 Aβ42 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 Aβ42 content in the brain.

AB - The N1411 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 β-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 β-protein (Aβ) 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 Aβ42 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 Aβ42 content in the brain.

KW - Alzheimer's disease

KW - Amyloid β-protein

KW - Presenilin 2

KW - Transgenic mouse

UR - http://www.scopus.com/inward/record.url?scp=18544411933&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18544411933&partnerID=8YFLogxK

M3 - Article

C2 - 9648880

AN - SCOPUS:18544411933

VL - 71

SP - 313

EP - 322

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 1

ER -