OVEREXPRESSION OF BCL-2 IN TRANSGENIC MICE PROTECTS NEURONS FROM NATURALLY-OCCURRING CELL-DEATH AND EXPERIMENTAL-ISCHEMIA

被引:1008
作者
MARTINOU, JC
DUBOISDAUPHIN, M
STAPLE, JK
RODRIGUEZ, I
FRANKOWSKI, H
MISSOTTEN, M
ALBERTINI, P
TALABOT, D
CATSICAS, S
PIETRA, C
HUARTE, J
机构
[1] UNIV GENEVA,CTR MED,DEPT PHYSIOL,CH-1211 GENEVA,SWITZERLAND
[2] UNIV GENEVA,CTR MED,DEPT PATHOL,CH-1211 GENEVA,SWITZERLAND
[3] UNIV GENEVA,CTR MED,DEPT MORPHOL,CH-1211 GENEVA,SWITZERLAND
[4] GLAXO SPA,DEPT PHARMACOL,I-37100 VERONA,ITALY
关键词
D O I
10.1016/0896-6273(94)90266-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Naturally occurring cell death (NOCD) is a prominent feature of the developing nervous system. During this process, neurons express bcl-2, a major regulator of cell death whose expression may determine whether a neuron dies or survives. To gain insight into the possible role of bcl-2 during NOCD in vivo, we generated lines of transgenic mice in which neurons overexpress the human BCL-2 protein under the control of the neuron-specific enolase (NSE) or phosphoglycerate kinase (PCK) promoters. BCL-2 overexpression reduced neuronal loss during the NOCD period, which led to hypertrophy of the nervous system. For instance, the facial nucleus and the ganglion cell layer of the retina had, respectively, 40% and 50% more neurons than normal. Consistent with this finding, more axons than normal were found in the facial and optic nerves. We also tested whether neurons overexpressing BCL-2 were more resistant to permanent ischemia induced by middle cerebral artery occlusion; in transgenic mice, the volume of the brain infarction was reduced by 50% as compared with wildtype mice. These animals represent an invaluable tool for studying the effects of increased neuronal numbers on brain function as well as the mechanisms that control the survival of neurons during development and adulthood.
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页码:1017 / 1030
页数:14
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