Adult Apaf-1-deficient mice exhibit male infertility
Adult Apaf-1-deficient mice exhibit male infertility
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DOI：
10.1006/dbio.1999.9585
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发表时间：
2000-02-15
影响因子：
2.7
通讯作者：
Herz, J
中科院分区：
文献类型：
--
作者：
Honarpour, N;Du, CY;Herz, J
细胞色素c从线粒体释放，并随后与凋亡蛋白激活因子-1(APAF-1)结合，是细胞凋亡事件的关键触发因素。由APAF-1、dATP和细胞色素c组成的复合体激活一系列被称为caspase的细胞质蛋白水解酶，导致细胞凋亡。我们已经破坏了小鼠的APAF-1基因。像以前关于这种基因敲除模型的报道一样，我们发现大多数APAF-1突变体在围产期死亡，并且经常表现为脑外畸形和颅裂。我们还发现，在基因敲除中发展的神经损伤是由于神经前体细胞过多，早在胚胎发育的9.5天就表现出来。与之前关于APAF-1基因敲除小鼠的报告相反，我们发现5%的突变体成功地存活到成年。在这些幸存者中，大脑发育正常，但在男性中，精原细胞退化，导致几乎没有精子。因此，细胞色素c介导的细胞凋亡并不是正常神经发育所必需的，但对精子发生是必不可少的。这些发现强烈表明，替代的凋亡途径与APAF-1协同工作，并平行于APAF-1，并可以改变其对程序性细胞死亡的影响，(C)2000学术出版社。
Release of cytochrome c from the mitochondria, and subsequent binding to apoptotic protease-activating factor-1 (Apaf-1), is a key trigger of apoptotic events. A complex composed of Apaf-1, dATP, and cytochrome c activates a series of cytoplasmic proteases called caspases, leading to apoptotic cell death. We have disrupted the Apaf-1 gene in the mouse. Like previous reports on this knockout model, we find that most Apaf-1 mutants die perinatally and frequently exhibit exencephaly and cranioschesis. We additionally find that the neural lesions that develop in the knockout are due to an excess of neural progenitor cells that manifests as early as embryonic day 9.5 in development. In contrast to previous reports on the Apaf-1 knockout mice, we find that 5% of the mutants successfully survive to adulthood. In these survivors, the brain develops normally, but in males, there is degeneration of spermatogonia resulting in the virtual absence of sperm. Thus, cytochrome c-mediated apoptosis is not absolutely required for normal neural development, but is essential for spermatogenesis. These findings strongly suggest that alternative apoptotic pathways work in conjunction with and parallel to Apaf-1 and can modify its effect on programmed cell death, (C) 2000 Academic Press.