Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2

被引：23

作者：

Azkona, G. ^{[1
,2
,3
]}

Amador-Arjona, A. ^{[1
,2
]}

Obradors-Tarrago, C. ^{[1
,2
]}

Varea, E. ^{[4
,5
]}

Arque, G. ^{[1
,2
]}

Pinacho, R. ^{[1
]}

Fillat, C. ^{[1
,2
]}

de la Luna, S. ^{[1
,2
,6
]}

Estivill, X. ^{[1
]}

Dierssen, M. ^{[1
,2
]}

机构：

[1] CRG, Genes & Dis Program, Barcelona 08003, Spain

[2] CIBERER, E-08003 Barcelona, Catalonia, Spain

[3] Univ Basque Country UPV EHU, Dept Neurosci, E-48003 Bizkaia, Spain

[4] Univ Miguel Hernandez, Dept Histol, E-03550 Alicante, Spain

[5] Univ Miguel Hernandez, Dept Anat, E-03550 Alicante, Spain

[6] ICREA, Barcelona, Catalonia, Spain

来源：

GENES BRAIN AND BEHAVIOR | 2010年 / 9卷 / 02期

关键词：

Down syndrome; Alzheimer disease; BACE2; chromosome; 21; noradrenergic system; locus coeruleus; AMYLOID PRECURSOR PROTEIN; DOWN-SYNDROME; ALZHEIMERS-DISEASE; TS65DN MICE; BEHAVIORAL-ASSESSMENT; ASPARTYL PROTEASE; ALPHA-SECRETASE; TRANSGENIC MICE; LOCUS-COERULEUS; BRAIN;

D O I：

10.1111/j.1601-183X.2009.00538.x

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

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.

引用

页码：160 / 172

页数：13

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