Behavioral alterations associated with apoptosis and down-regulation of presenilin 1 in the brains of p53-deficient mice
Behavioral alterations associated with apoptosis and down-regulation of presenilin 1 in the brains of p53-deficient mice
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DOI：
10.1073/pnas.97.10.5346
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发表时间：
2000-05-09
影响因子：
11.1
通讯作者：
Telerman, A
中科院分区：
文献类型：
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作者：
Amson, R;Lassalle, JM;Telerman, A
早老素1(PS1)的表达受抑癌基因P53的抑制。研究表明，野生型PS1是一种有效的抗细胞凋亡分子，能够显著抑制P53依赖和P53非依赖的细胞死亡。我们在功能和分子水平上分析了p53基因敲除小鼠的大脑。令人惊讶的是，我们发现，缺乏P53表达会导致脑组织细胞凋亡，并伴随着学习障碍和行为改变。P53基因缺陷的小鼠表现出意外的p21(Waf1)过度表达，随后他们大脑中PS1的表达下调。这一过程是渐进的，与年龄有关。这些数据表明，P53通路除了影响肿瘤抑制外，可能在调节大脑中的神经行为功能和细胞生存方面发挥重要作用。
Presenilin 1 (PS1) expression is repressed by the p53 tumor suppressor. As shown herein, wild-type PS1 is an effective antiapoptotic molecule capable of significantly inhibiting p53-dependent and p53-independent cell death. We analyzed, at the functional and molecular levels, the brains of p53 knockout mice. Surprisingly, we found that lack of p53 expression induces apoptotic brain lesions, accompanied by learning deficiency and behavioral alterations. p53-deficient mice show an unexpected overexpression of p21(waf1) with subsequent down-regulation of PS1 in their brains. This process is progressive and age-dependent. These data indicate that the p53 pathway, besides affecting tumor suppression, may play a major role in regulating neurobehavioral function and cell survival in the brain.