Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver

Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver
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DOI:
10.1126/science.292.5521.1546
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发表时间:
2001-05-25
期刊:
影响因子:
56.9
通讯作者:
Nagata, S
Nagata, S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kawane, K;Fukuyama, H;Nagata, S

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哺乳动物的成熟红细胞没有核,尽管它们从有核的前体细胞分化而来。去核发生的机制还不是很清楚。在这里,我们证明了脱氧核糖核酸酶II(DNase II)对于小鼠胎肝中确定的红细胞生成是必不可少的。由于严重的贫血,没有活的DNA酶II缺失的小鼠出生。当突变的胎肝细胞被转移到致死照射的野生型小鼠中时,突变的细胞产生了成熟的红细胞,这表明DNaseII以非细胞自主的方式发挥作用。组织化学分析表明,DNA酶II的关键细胞来源是胎儿肝脏中确定的红细胞生成部位的巨噬细胞。因此,巨噬细胞中的DNA酶II似乎负责破坏从红系前体细胞中排出的核DNA。
Mature erythrocytes in mammals have no nuclei, although they differentiate from nucleated precursor cells. The mechanism by which enucleation occurs is not well understood. Here we show that deoxyribonuclease II (DNase II) is indispensable for definitive erythropoiesis in mouse fetal liver. No live DNase Ii-null mice were born, owing to severe anemia. When mutant fetal liver cells were transferred into Lethally irradiated wild-type mice, mature red blood cells were generated from the mutant cells, suggesting that DNase II functions in a non-cell-autonomous manner. Histochemical analyses indicated that the critical cellular sources of DNase II are macrophages present at the site of definitive erythropoiesis in the fetal Liver. Thus, DNase II in macrophages appears to be responsible for destroying the nuclear DNA expelled from erythroid precursor cells.