Skeletal and CNS defects in Presenilin-1-deficient mice
Skeletal and CNS defects in Presenilin-1-deficient mice
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DOI：
10.1016/s0092-8674(00)80244-5
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发表时间：
1997-05-16
期刊：
影响因子：
64.5
通讯作者：
Tonegawa, S
中科院分区：
文献类型：
--
作者：
Shen, J;Bronson, RT;Tonegawa, S
早老素-1 （PS1）是早发性熟悉性阿尔茨海默病（FAD）的主要基因。为了了解PS1的正常功能，我们在PS1的小鼠同源物中产生了一个靶向零突变。我们报道PS1（-/-）小鼠在自然分娩或剖腹产后不久死亡。纯合突变体的骨骼严重变形。PS1空突变体的中枢神经系统出血的位置、严重程度和发病时间各不相同。PS1（-/-）脑的心室区在胚胎14.5天明显变薄，表明神经发生受损。胚期16.5后，突变体大脑特定亚区大量神经元丢失引起的双侧脑空化非常突出。这些结果表明PS1对于轴骨的正常形成、正常的神经发生和神经元存活是必需的。
Presenilin-1 (PS1) is the major gene responsible for early-onset familiar Alzheimer's disease (FAD). To understand the normal function of PS1, we have generated a targeted null mutation in the murine homolog of PS1. We report that PS1(-/-) mice die shortly after natural birth or Caesarean section. The skeleton of homozygous mutants is grossly deformed. Hemorrhages occur in the CNS of PS1 null mutants with varying location, severity, and time of onset. The ventricular zone of PS1(-/-) brains is markedly thinner by embryonic day 14.5, indicating an impairment in neurogenesis. Bilateral cerebral cavitation caused by massive neuronal loss in specific subregions of the mutant brain is prominent after embryonic day 16.5. These results show that PS1 is required for proper formation of the axial skeleton, normal neurogenesis, and neuronal survival.