Variation in gene expression and aberrantly regulated chromosome regions in cloned mice

Variation in gene expression and aberrantly regulated chromosome regions in cloned mice
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DOI:
10.1095/biolreprod.105.044958
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发表时间:
2005-12-01
影响因子:
3.6
通讯作者:
Ishino, F
Ishino, F
中科院分区:
生物学2区
文献类型:
--
作者:
Kohda, T;Inoue, K;Ishino, F

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DNA 微阵列分析用于确定源自支持细胞和卵丘细胞的体细胞克隆小鼠的精确全基因组基因表达谱。尽管新生克隆小鼠的外观和遗传特性正常,但它却显示出出乎意料的巨大表观遗传多样性。在克隆小鼠的三个新生组织中,与正常对照相比,9-40%的检测基因的表达以供体细胞依赖性或非依赖性方式升高或降低两倍以上。在两种类型的克隆中,相对较少(0.4-4%)的基因以相同的方式表现出上调或下调。对基因表达变异的聚类分析确定了体细胞克隆中基因表达受到异常控制的几个染色体区域。这些结果使人们更全面地了解体细胞克隆彼此之间以及与有性生殖产生的正常个体之间的差异,并表明体细胞克隆在再生医学中的应用面临着重大困难。
DNA microarray analysis was used to determine the precise genome-wide gene expression profiles of somatic cloned mice derived from Sertoli and cumulus cells. It demonstrated unexpectedly large epigenetic diversity in neonatal cloned mice, despite their normal appearance and genetic identity. In three neonatal tissues of the cloned mice, the expression of 9-40% of the genes examined was more than two times higher or lower in donor cell-dependent or -independent manners compared with normal controls. Relatively few (0.4-4%) of the genes exhibited up- or downregulation in the same manner in both types of clone. A cluster analysis of the variation in gene expression led to the identification of several chromosome regions in which gene expression was aberrantly controlled in the somatic clones. These results provide a more complete understanding of how somatic clones differ from each other and from normal individuals produced by sexual reproduction and indicate the significant difficulties that face the application of somatic cloning in regenerative medicine.