Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2.
BACE2 is homologous to BACE1, a beta-secretase that is involved in the amyloidogenic pathway of amyloid precursor protein (APP), and maps to the Down syndrome critical region of chromosome 21. Alzheimer disease neuropathology is common in Down syndrome patients at relatively early ages, and it has thus been speculated that BACE2 co-overexpression with APP would promote the early neurodegenerative phenotype. However, the in vivo function of BACE2 has not yet been elucidated. The aim of the present work has been to analyse the impact of in vivo BACE2 overexpression using a transgenic mouse model. Our results suggest that BACE2 is not involved in the amyloidogenic pathway, cognitive dysfunction or cholinergic degeneration. However, TgBACE2 animals showed increased anxiety-like behaviour along with increased numbers of noradrenergic neurones in locus coeruleus, thus suggesting an unexpected role of BACE2 overexpression.
Azkona
G
G
Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), E-08003 Barcelona, Catalonia, Spain.
Amador-Arjona
A
A
Obradors-Tarragó
C
C
Varea
E
E
Arqué
G
G
Pinacho
R
R
Fillat
C
C
de la Luna
S
S
Estivill
X
X
Dierssen
M
M
D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D000818:Animals; D001007:Anxiety / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D003624:Darkness; D004314:Down Syndrome / Q000201:enzymology / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000473:pathology; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000473:pathology; D010787:Photosensitivity Disorders / Q000235:genetics; D016548:Prosencephalon / Q000201:enzymology; D012313:RNA / Q000235:genetics; D014158:Transcription, Genetic
C509285:Bace2 protein, mouse; D012313:RNA; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509282:Bace1 protein, mouse