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小鼠辐射诱导的急性髓系白血病细胞中通过插入脑池内A颗粒元件出现异常长的靶序列重复。

Unusual long target duplication by insertion of intracisternal A-particle element in radiation-induced acute myeloid leukemia cells in mouse.

作者信息

Tanaka I, Ishihara H

机构信息

Bioregulation Research Group, National Institute of Radiological Sciences, Chiba, Japan.

出版信息

FEBS Lett. 1995 Dec 4;376(3):146-50. doi: 10.1016/0014-5793(95)01262-2.

DOI:10.1016/0014-5793(95)01262-2
PMID:7498529
Abstract

Retrotransmission into the IL-3/GM-CSF gene locus by the retrotransposon intracisternal A-particle (IAP) had been observed in distinct tumor cell lines. We analyzed the locus in genomes from 7 different myeloid leukemia cell strains which were originally generated by whole-body X-irradiation of the inbred C3H/He mice at a dose of 3 Gy and maintained by in vivo passage. In one leukemia cell strain out of 7 such cases, RFLP of an allele of the interleukin-3 gene was found. Sequence analysis after cloning from the genomic library showed that a type I delta 2 IAP element was inserted in the region upstream of the IL-3 gene in the head-to-head orientation. This suggests that the locus in myeloid cells is sensitive for integration of IAP elements. Additionally, an unusual long target duplication of 82 bp, 14-fold larger than normal one, was found at the junction of the element. This suggests the possibility of a radiation-induced integration mechanism which is distinct from normal retrotransmission.

摘要

在不同的肿瘤细胞系中已观察到逆转座子脑内A颗粒(IAP)向白细胞介素-3/粒细胞-巨噬细胞集落刺激因子(IL-3/GM-CSF)基因座的逆转录转座。我们分析了7种不同髓系白血病细胞株基因组中的该基因座,这些细胞株最初是通过对近交系C3H/He小鼠进行3 Gy的全身X射线照射产生的,并通过体内传代进行维持。在7个这样的病例中的1个白血病细胞株中,发现了白细胞介素-3基因一个等位基因的限制性片段长度多态性(RFLP)。从基因组文库克隆后进行的序列分析表明,一个I型δ2 IAP元件以头对头的方向插入到IL-3基因上游区域。这表明髓系细胞中的该基因座对IAP元件的整合敏感。此外,在元件的连接处发现了一个异常长的82 bp的靶序列重复,比正常的大14倍。这表明存在一种不同于正常逆转录转座的辐射诱导整合机制的可能性。

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引用本文的文献

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Microarray-based global mapping of integration sites for the retrotransposon, intracisternal A-particle, in the mouse genome.基于微阵列技术对小鼠基因组中逆转录转座子——脑内A颗粒(intracisternal A-particle)整合位点的全基因组图谱绘制。
Nucleic Acids Res. 2008 Jun;36(10):e59. doi: 10.1093/nar/gkn235. Epub 2008 May 1.
2
Intracisternal A-particle element transposition into the murine beta-glucuronidase gene correlates with loss of enzyme activity: a new model for beta-glucuronidase deficiency in the C3H mouse.脑池内A颗粒元件转位至小鼠β-葡萄糖醛酸酶基因与酶活性丧失相关:C3H小鼠β-葡萄糖醛酸酶缺乏症的新模型。
Mol Cell Biol. 1998 Nov;18(11):6474-81. doi: 10.1128/MCB.18.11.6474.