title: NSE-controlled carboxyl-terminus of APP gene over-expressing in transgenic mice induces altered expressions in behavior, Abeta-42, and GSK3beta binding proteins.
abstract: The amyloid protein precursor (APP) is cleaved in its intramembranous domain by gamma-secrease to generate amyloid beta and a free carboxyl-terminal intracellular fragment. The carboxyl-terminal of 105 amino acids of APP (APP-C105) plays a crucial role in the neuropathology of Alzheimer's disease (AD), but it is incompletely understand how APP-C105 overexpression interacts and regulates the brain function and Abeta-42 levels, and whether or not it is associated with the expressions of GSK3beta-binding proteins. To test this, transgenic mice expressing NSE-controlled APP-C105 were produced and tested for their above phenotypes. A behavioral deficit was observed in the 9 months old transgenic mice, and western blot indicated that there was a predominant expression of APP-C105 in transgenic brains compared with those of non-transgenic brains. In parallel, APP-C105 overexpression resulted in the modulation of the Abeta-42 level, gamma-secretase activity, GSK3beta-binding proteins including PS1, tau, and beta-catenin in the brains of the transgenic mice relative to the non-transgenic mice. Thus, altered expressions of these neuropathological phenotypes in APP-C105 transgenic mice could be useful targets in developing new therapeutic treatments.
authors.affiliation: Division of Laboratory Animal Resources, Korea Food and Drug Administration, National Institute of Toxicological Research, 5 Nokbun-dong Eunpyng-ku, Seoul 122-704, Republic of Korea.
authors.forename: Hwa J
authors.initials: HJ
authors.lastname: Lim
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: Dae Y
authors.initials: DY
authors.lastname: Hwang
authors.forename: Seung W
authors.initials: SW
authors.lastname: Jee
authors.forename: Su H
authors.initials: SH
authors.lastname: Lee
authors.forename: Yhun Y
authors.initials: YY
authors.lastname: Sheen
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*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000502:physiology; D017434:Protein Structure, Tertiary; D019076:Transgenes / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D010751:Phosphopyruvate Hydratase