Abnormal regulation of DNA methyltransferase expression in cloned mouse embryos
Abnormal regulation of DNA methyltransferase expression in cloned mouse embryos
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DOI：
10.1095/biolreprod.102.014076
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发表时间：
2003-07-01
影响因子：
3.6
通讯作者：
Latham, KE
中科院分区：
文献类型：
--
作者：
Chung, YG;Ratnam, S;Latham, KE
通过体细胞核移植进行克隆是低效的。这一点在几乎所有胚胎和胎儿发育阶段存活的克隆后代数量的显著减少中显而易见。我们发现，克隆植入前小鼠胚胎异常表达体细胞形式的Dnmt 1 DNA（胞嘧啶-5）甲基转移酶，其表达通常是由转录后机制阻止。此外，母体卵母细胞衍生的Dnmt 1 o亚型在八细胞阶段很少或没有发生预期的易位到胚胎核。Dnmt 1 s和Dnmt 1 o表达和细胞质-核运输的调节中的这种缺陷可能会阻止克隆完成必要的早期发育事件。此外，异常的Dnmt 1定位和表达可能导致DNA甲基化缺陷和克隆哺乳动物中观察到的发育异常。
Cloning by somatic cell nuclear transfer is inefficient. This is evident in the significant attrition in the number of surviving cloned offspring at virtually all stages of embryonic and fetal development. We find that cloned preimplantation mouse embryos aberrantly express the somatic form of the Dnmt1 DNA (cytosine-5) methyltransferase, the expression of which is normally prevented by a posttranscriptional mechanism. Additionally, the maternal oocyte-derived Dnmt1o isoform undergoes little or none of its expected translocation to embryonic nuclei at the eight-cell stage. Such defects in the regulation of Dnmt1s and Dnmt1o expression and cytoplasmic-nuclear trafficking may prevent clones from completing essential early developmental events. Furthermore, aberrant Dnmt1 localization and expression may contribute to the defects in DNA methylation and the developmental abnormalities seen in cloned mammals.