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缺乏DNA片段化因子45的小鼠对DNA片段化和染色质浓缩的抗性

Resistance to DNA fragmentation and chromatin condensation in mice lacking the DNA fragmentation factor 45.

作者信息

Zhang J, Liu X, Scherer D C, van Kaer L, Wang X, Xu M

机构信息

Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

出版信息

Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12480-5. doi: 10.1073/pnas.95.21.12480.

Abstract

The DNA fragmentation factor 45 (DFF45) is a subunit of a heterodimeric nuclease complex critical for the induction of DNA fragmentation in vitro. To understand the in vivo role of DFF45 in programmed cell death, we generated DFF45 mutant mice. DNA fragmentation activity is completely abolished in cell extracts from DFF45 mutant tissues. In response to apoptotic stimuli, splenocytes, thymocytes, and granulocytes from DFF45 mutant mice are resistant to DNA fragmentation, and splenocytes and thymocytes are also resistant to chromatin condensation. Nevertheless, development of the immune system in the DFF45 mutant mice is normal. These results demonstrate that DFF45 is critical for the induction of DNA fragmentation and chromatin condensation in vivo, but is not required for normal immune system development.

摘要

DNA片段化因子45(DFF45)是一种异二聚体核酸酶复合物的亚基,对体外DNA片段化的诱导至关重要。为了解DFF45在程序性细胞死亡中的体内作用,我们培育了DFF45突变小鼠。DFF45突变组织的细胞提取物中的DNA片段化活性完全丧失。响应凋亡刺激时,DFF45突变小鼠的脾细胞、胸腺细胞和粒细胞对DNA片段化具有抗性,脾细胞和胸腺细胞对染色质浓缩也具有抗性。然而,DFF45突变小鼠的免疫系统发育正常。这些结果表明,DFF45对体内DNA片段化和染色质浓缩的诱导至关重要,但正常免疫系统发育并不需要它。

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