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

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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 1
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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  • Cite this

    Oyama, F., Sawamura, N., Kobayashi, K., Morishima-Kawashima, M., Kuramochi, T., Ito, M., Tomita, T., Maruyama, K., Saido, T. C., 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, 71(1), 313-322.