Generation and characterization of endonuclease G null mice

Generation and characterization of endonuclease G null mice
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DOI:
10.1128/mcb.25.1.294-302.2005
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发表时间:
2005-01-01
影响因子:
5.3
通讯作者:
Lieber, MR
Lieber, MR
中科院分区:
生物学2区
文献类型:
--
作者:
Irvine, RA;Adachi, N;Lieber, MR

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核酸内切酶 G (endo G) 是真核细胞中最丰富的核酸酶之一。它在细胞核中编码并输入线粒体膜间隙。该核酸酶对单链和双链 DNA 均具有活性。我们从基因上破坏了小鼠的内切G基因,但没有干扰与内切G基因尾对尾定位的未知功能的保守重叠基因。在这些小鼠中,未检测到内切 G 蛋白的产生,并且破坏消除了内切 G 的核酸酶活性。内切 G 的缺失对前五代中的线粒体 DNA 拷贝数、结构或突变率没有影响。在标准细胞凋亡检测中,对核 DNA 降解也没有明显影响。内切G缺失小鼠是可存活的,并且在解剖学或组织学上没有显示出与年龄相关的或世代异常。我们推断,这种高度保守的蛋白质不具有可以通过此处描述的测定法辨别的线粒体或细胞凋亡功能,并且它可能具有尚未确定的功能。其他人最近报道的endo G缺失小鼠的早期胚胎致死可能是由于与endo G基因重叠的基因被破坏所致。
Endonuclease G (endo G) is one of the most abundant nucleases in eukaryotic cells. It is encoded in the nucleus and imported to the mitochondrial intermembrane space. This nuclease is active on single- and double-stranded DNA. We genetically disrupted the endo G gene in mice without disturbing a conserved, overlapping gene of unknown function that is oriented tail to tail with the endo G gene. In these mice, the production of endo G protein is not detected, and the disruption abolishes the nuclease activity of endo G. The absence of endo G has no effect on mitochondrial DNA copy number, structure, or mutation rate over the first five generations. There is also no obvious effect on nuclear DNA degradation in standard apoptosis assays. The endo G null mice are viable and show no age-related or generational abnormalities anatomically or histologically. We infer that this highly conserved protein has no mitochondrial or apoptosis function that can discerned by the assays described here and that it may have a function yet to be determined. The early embryonic lethality of endo G null mice recently reported by others may be due to the disruption of the gene that overlaps the endo G gene.