Elevated DNA double strand breaks and apoptosis in the CNS of scid mutant mice.
Elevated DNA double strand breaks and apoptosis in the CNS of scid mutant mice.
复制标题
scid 突变小鼠中枢神经系统 DNA 双链断裂和细胞凋亡升高。
DOI：
10.1038/sj.cdd.4400806
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发表时间：
2001
影响因子：
12.4
通讯作者：
Naegele,JR
中科院分区：
文献类型：
--
作者：
Vemuri,MC;Schiller,E;Naegele,JR
遗传学方法提供的证据表明，DNA末端连接问题在哺乳动物胚胎发育过程中的神经元存活中起着至关重要的作用。在目前的研究中，我们测试了DNA修复酶，DNA依赖的蛋白激酶，是否在小鼠大脑皮质神经元的存活中发挥重要作用。DNA-PK由一个称为Ku的DNA结合亚基和一个称为DNA-PKcs的催化亚基组成。在带有SCID突变的小鼠中，DNA-PKcs在接近激活域的位置被截断，这导致了激酶活性的丧失。我们比较了SCID和同基因野生型胚胎神经细胞死亡的空间和时间方面，发现SCID小鼠的死亡细胞显著增加，通过核变化、DNA片段化和caspase-3活性来评估。另外的生化和免疫细胞化学研究表明，在所研究的几种DNA修复酶中，只有SCID小鼠的PARP增加，这可能是对DNA链断裂的反应。细胞死亡与分化(2001)8,245-255
Genetic approaches have provided evidence that DNA end-joining problems serve an essential role in neuronal survival during development of mammalian embryos. In the present study, we tested whether the DNA repair enzyme, DNA dependent protein kinase, plays an important role in the survival of cerebral cortical neurons in mice. DNA-PK is comprised of a DNA-binding subunit called Ku and a catalytic subunit called DNA-PKcs. In mice with the scid mutation, DNA-PKcs is truncated near the kinase domain, which causes loss of kinase activity. We compared the spatial and temporal aspects of neuronal cell death in scid versus isogenic wild-type embryos and found a significant increase in dying cells in scid mice, as assessed by nuclear changes, DNA fragmentation and caspase-3 activity. Additional biochemical and immunocytochemical studies indicated that of several DNA repair enzymes investigated, only PARP was increased in scid mice, possibly in response to elevated DNA strand breaks. Cell Death and Differentiation (2001) 8, 245–255