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具有先天性染色体畸变的小鼠品系中的端粒缩短

Telomere shortening in mouse strains with constitutional chromosomal aberrations.

作者信息

Modino S, Slijepcevic P

机构信息

Brunel Institute of Cancer Genetics and Pharmacogenomics, Brunel University, Uxbridge, UK.

出版信息

Int J Radiat Biol. 2002 Sep;78(9):757-64. doi: 10.1080/09553000210146563.

DOI:10.1080/09553000210146563
PMID:12428916
Abstract

PURPOSE

To compare telomere length in mouse strains with constitutional chromosomal aberrations generated either by exposure of parents to ionizing radiation, a chemical mutagen or arising spontaneously with that of the karyotypically normal mouse from the same genetic background.

MATERIALS AND METHODS

Telomere length was assessed in five independently derived strains of mouse with constitutional chromosomal aberrations and in the karyotypically normal control mouse using quantitative fluorescence in situ hybridization (Q-FISH). Bone marrow cells obtained directly from the animals were used for the analysis.

RESULTS

Chromosomal aberrations, one in each mouse strain, included three reciprocal translocations induced by ionizing radiation, one insertion induced by a chemical mutagen and one spontaneous Robertsonian translocation. There was no cytogenetically detectable loss of material in any of the strains and most mice were phenotypically normal. Telomeres were significantly shorter in all mouse strains with constitutional chromosomal aberrations in comparison with those originating from the karyatypically normal mouse from the same genetic background. Telomeres were significantly shorter at p-arms than at q-arms in all animals. The telomere length in individual chromosomes was variable and there was no single chromosome with consistently short telomeres in all animals.

CONCLUSIONS

The presence of stable chromosomal aberrations, such as translocations or insertions, in the mouse genome may generate telomere shortening. This might have implications for understanding biological consequences or radiation-induced stable chromosomal aberrations.

摘要

目的

比较因亲本暴露于电离辐射、化学诱变剂或自发产生而具有染色体结构异常的小鼠品系与来自相同遗传背景的核型正常小鼠的端粒长度。

材料与方法

使用定量荧光原位杂交(Q-FISH)技术,对五个独立衍生的具有染色体结构异常的小鼠品系以及核型正常的对照小鼠进行端粒长度评估。直接从动物获取的骨髓细胞用于分析。

结果

每个小鼠品系中均存在一种染色体结构异常,其中包括三种由电离辐射诱导的相互易位、一种由化学诱变剂诱导的插入以及一种自发的罗伯逊易位。所有品系在细胞遗传学上均未检测到物质丢失,且大多数小鼠表型正常。与来自相同遗传背景的核型正常小鼠相比,所有具有染色体结构异常的小鼠品系的端粒均显著缩短。在所有动物中,端粒在p臂比在q臂显著更短。单个染色体的端粒长度存在差异,且在所有动物中没有一条染色体的端粒始终较短。

结论

小鼠基因组中稳定染色体结构异常(如易位或插入)的存在可能导致端粒缩短。这可能对理解生物学后果或辐射诱导的稳定染色体结构异常具有重要意义。

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