title: Early changes in behavior deficits, amyloid beta-42 deposits and MAPK activation in doubly transgenic mice co-expressing NSE-controlled human mutant PS2 and APPsw.
abstract: 1. Doubly transgenic mice were some differences in the period proceeding of the development of Abeta-42 deposits and behavioral deficits. It was not characterized human mutant PS2 (hPS2) with APPsw in the brains of double transgenic mice. The aim of this study was to examine whether doubly transgenic mice co-expressing NSE-controlled APPsw and hPS2m develop AD-like phenotypes much earlier than singly APPsw or hPS2m alone. 2. We produced doubly transgenic mice from a cross between our previously created NSE-controlled hPS2m and an APPsw transgenic line. This doubly transgenic line was quantitatively produced by cross with age-matched control mice, and the produced mice were separated into 5, 6, 7 and 8-month old age groups. At the age of 8 months, the four groups of mice were tested for behavioral function, levels of Abeta-42 deposition, and potential signaling events. 3. It was shown that all the AD-like phenotypes, including behavior deficits, Abeta-42 levels, MAPK activation and ER expressions in doubly transgenic mice develop much earlier in the early time of AD development than their singly transgenic and non-transgenic littermates. 4. The results suggest that elevated Abeta-42 levels, and MAPK activation in doubly transgenic mice are model for early diagnosis and treatment of AD with therapeutic drug.
authors.affiliation: Division of Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA, 5 Nokbun-dong Eunpyng-ku, Seoul, 122-704, Korea.
authors.forename: Dae Y
authors.initials: DY
authors.lastname: Hwang
authors.forename: Jung S
authors.initials: JS
authors.lastname: Cho
authors.forename: Jae H
authors.initials: JH
authors.lastname: Oh
authors.forename: Sun B
authors.initials: SB
authors.lastname: Shim
authors.forename: Seung W
authors.initials: SW
authors.lastname: Jee
authors.forename: Su H
authors.initials: SH
authors.lastname: Lee
authors.forename: Su J
authors.initials: SJ
authors.lastname: Seo
authors.forename: Chi W
authors.initials: CW
authors.lastname: Song
authors.forename: Seok H
authors.initials: SH
authors.lastname: Lee
authors.forename: Yong K
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000235:genetics*; D053766:Presenilin-2; D011401:Promoter Regions, Genetic / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D053766:Presenilin-2; C075222:amyloid beta-protein (1-42); D010751:Phosphopyruvate Hydratase