Targeted disruption of the mouse ELYS gene results in embryonic death at peri-implantation development

Targeted disruption of the mouse ELYS gene results in embryonic death at peri-implantation development
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DOI:
10.1111/j.1365-2443.2004.00791.x
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发表时间:
2004-11-01
期刊:
影响因子:
2.1
通讯作者:
Taga, T
Taga, T
中科院分区:
生物学4区
文献类型:
--
作者:
Okita, K;Kiyonari, H;Taga, T

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小鼠的早期发育是一个复杂的过程,受包括转录因子在内的多种蛋白质的调控。最近,我们确定了一个假定的转录因子,ELYS(胚胎大分子来自卵黄囊),使用减法策略。为了阐明ELYS在体内的作用,我们通过同源重组产生了ELYS缺陷小鼠。尽管杂合子小鼠看起来是健康的、可生育的和正常的,但ELYS突变的纯合子胚胎在胚胎日(E)3.5和5.5之间死亡。在E3.5从子宫收集的突变体囊胚是活的,与野生型同窝仔难以区分。然而,当在体外培养时,由于凋亡,它们显示出内部细胞的增殖受损。ELYS mRNA的表达检测在内细胞团(ICM)和滋养外胚层在囊胚期,并持续在整个发育中的胚胎在E4.5至6.5。这些结果表明,ELYS是小鼠早期发育的关键因素,对内细胞的存活至关重要。
Early mouse development is a complicated process that is controlled by various proteins including transcription factors. Recently, we identified a putative transcription factor, ELYS (embryonic large molecule derived from yolk sac), using a subtraction strategy. To elucidate the role of ELYS in vivo, we generated ELYS-deficient mice by homologous recombination. Although heterozygous mice appeared to be healthy, fertile and normal, embryos homozygous for the ELYS mutation died between embryonic day (E) 3.5 and 5.5. Null mutant blastocysts collected from the uterus at E3.5 were viable and indistinguishable from wild-type littermates. However, when cultured in vitro, they showed impaired proliferation of the inner cells, because of apoptosis. The expression of ELYS mRNA was detected in both the inner cell mass (ICM) and the trophectoderm at the blastocyst stage, and persisted throughout the developing embryo during E4.5 to 6.5. These results indicate that ELYS is a critical factor for early mouse development and is essential for the survival of the inner cells.