title: Pen-2 overexpression induces Aβ-42 production, memory defect, motor             activity enhancement and feeding behavior dysfunction in NSE/Pen-2 transgenic             mice.
abstract: Pen-2 is a key regulator of the γ-secretase complex, which is involved in the production of the amyloid β (Aβ)-42 peptides, which ultimately lead to Alzheimer's disease (AD). While Pen-2 has been studied in vitro, Pen-2 function in vivo in the brains of transgenic (Tg) mice overexpressing human Pen-2 (hPen-2) protein has not been studied. This study aimed to determine whether Pen-2 overexpression could regulate the AD-like phenotypes in Tg mice. NSE/hPen-2 Tg mice were produced by the microinjection of the NSE/hPen-2 gene into the pronucleus of fertilized eggs. The expression of the hPen-2 gene under the control of the NSE promoter was successfully detected only in the brain and kidney tissue of NSE/hPen-2 Tg mice. Also, 12-month-old NSE/hPen-2 Tg mice displayed behavioral dysfunction in the water maze test, motor activity and feeding behavior dysfunction in food intake/water intake/motor activity monitoring system. In addition, tissue samples displayed dense staining with antibody to the Aβ-42 peptide. Furthermore, NSE/hPen-2 Tg mice exhibiting feeding behavior dysfunction were significantly more apt to display symptoms related to diabetes and obesity. These results suggest that Pen-2 overexpression in NSE/hPen-2 Tg mice may induce all the AD-like phenotypes, including behavioral deficits, motor activity and feeding behavior dysfunction, Aβ-42 peptide deposition and chronic disease induction.
authors.affiliation: Department of Biomaterial Science, College of Natural Resources                     and Life Science, Pusan National University, Miryang, Republic of Korea.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Nam
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Seo
authors.forename: Jun Seo
authors.initials: JS
authors.lastname: Goo
authors.forename: Jee Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Sun Il
authors.initials: SI
authors.lastname: Choi
authors.forename: Hae Ryun
authors.initials: HR
authors.lastname: Lee
authors.forename: In Sik
authors.initials: IS
authors.lastname: Hwang
authors.forename: Seung Wan
authors.initials: SW
authors.lastname: Jee
authors.forename: Su Hae
authors.initials: SH
authors.lastname: Lee
authors.forename: Chang Jun
authors.initials: CJ
authors.lastname: Bae
authors.forename: Jung Youn
authors.initials: JY
authors.lastname: Park
authors.forename: Hye Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Sun Bo
authors.initials: SB
authors.lastname: Shim
authors.forename: Dae Youn
authors.initials: DY
authors.lastname: Hwang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000235:genetics*; D005247:Feeding Behavior; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C469349:PSENEN protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases