日本研究人员在最新一期美国《科学》杂志网络版上发表论文说，如果X染色体上的一个基因异常发挥作用，体细胞克隆小鼠的出生率就会降低，而如果使这个基因不发挥作用，则可大幅提高克隆小鼠出生率。
体细胞克隆即从个体的皮肤等体细胞中取出细胞核，植入去除了细胞核的卵细胞，然后将生成的胚胎移植到代孕母亲的子宫内，最终诞生与提供体细胞的动物拥有同样遗传信息的克隆动物。虽然人类1996年就培育出了第一只体细胞克隆的哺乳动物绵羊多利，但此后克隆动物的出生率一直非常低。
日本理化研究所生物资源中心研究员小仓淳郎率领的研究小组，在分析利用克隆技术培育出的小鼠胚胎的基因时，发现在性染色体之一的X染色体上，基因“Xist”异常发挥作用。“Xist”基因能够抑制其他基因的功能。
研究人员使小鼠的“Xist”基因不再发挥作用，然后再用它们的体细胞培育克隆胚胎，结果克隆小鼠的出生率大幅提高，相当于以前水平的八九倍。
研究人员说，今后这项技术有望应用于畜产领域。
原文摘要：
Science DOI: 10.1126/science.1194174
Impeding Xist Expression from the Active X Chromosome Improves Mouse Somatic Cell Nuclear Transfer
Kimiko Inoue,1,2 Takashi Kohda,3 Michihiko Sugimoto,1 Takashi Sado,4 Narumi Ogonuki,1 Shogo Matoba,1 Hirosuke Shiura,1 Rieko Ikeda,1 Keiji Mochida,1 Takashi Fujii,5 Ken Sawai,5 Arie P. Otte,6 X. Cindy Tian,7 Xiangzhong Yang,7 Fumitoshi Ishino,3 Kuniya Abe,1,2 Atsuo Ogura1,2,8,*
Cloning mammals by somatic cell nuclear transfer (SCNT) is highly inefficient because of erroneous reprogramming of the donor genome. Reprogramming errors appear to arise randomly, but the nature of nonrandom, SCNT-specific errors remains elusive. We found that Xist, a noncoding RNA that inactivates one of the two X chromosomes in females, was ectopically expressed from the active X (Xa) chromosome in cloned mouse embryos of both sexes. Deletion of Xist on Xa showed in normal global gene expression and resulted in about an 8- to 9-fold increase in cloning efficiency. We also identified an Xist-independent mechanism that specifically downregulated a subset of X-linked genes through somatic-type repressive histone blocks. Thus, we have identified nonrandom reprogramming errors in mouse cloning that can be altered to improve the efficiency of SCNT methods.
1 BioResource Center, RIKEN, Tsukuba, Japan.
2 Graduate School of Life and Environmental Science, University of Tsukuba, Tsukuba, Japan.
3 Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
4 Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
5 Faculty of Agriculture, Iwate University, Iwate, Japan.
6 Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands.
7 Center for Regenerative Biology and Department of Animal Science, University of Connecticut, Connecticut 06269, USA.
8 The Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
