The acrosomal protein Dickkopf-like 1 (DKKL1) is not essential for fertility.

The acrosomal protein Dickkopf-like 1 (DKKL1) is not essential for fertility.
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DOI:
10.1016/j.fertnstert.2009.06.011
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发表时间:
2010-03-15
影响因子:
6.7
通讯作者:
DePamphilis ML
DePamphilis ML
中科院分区:
医学2区
文献类型:
--
作者:
Kaneko KJ;Kohn MJ;Liu C;DePamphilis ML

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为确定Dkkcl1基因对小鼠发育、存活率和生育力的影响,本研究以政府研究机构C57BL/6和129X1/SVJ品系小鼠以及C57BL/6和129X1/SVJ混合品系转基因小鼠为研究对象。构建的小鼠缺乏功能上的Dkkcl1基因。DNA、RNA和蛋白质分析证实了该基因的缺失;通过连续交配方案检查了体内的可育性。以前的研究表明,DKKL1是哺乳动物特有的基因,如果不是唯一的话,它主要在发育中的精母细胞中表达,DKKL1蛋白在成熟精子的顶体中积累。随后的研究表明,Dkkcl1也在滋养外胚层/胎盘谱系中表达。综上所述,这些结果有力地表明DKKL1蛋白是滋养层巨细胞或精子终末分化所必需的,这两者都直接与生育有关。为了挑战这一假说,有条件的靶向突变被用来去除小鼠的Dkkcl1基因。令人惊讶的是,尽管DKKL1蛋白的任何部分都不能产生DKKL1蛋白,DKKL1无效合子的胚胎还是发育成了有活力的、有生育能力的成年人。DKKL1是一种哺乳动物特有的顶体蛋白,对发育和生育都不是必需的。
To determine the role of Dkkl1 on mouse development, viability and fertility Prospective experimental study Government research institution Mice of C57BL/6 and 129X1/SvJ strains, as well as transgenic mice of mixed C57BL/6 and 129X1/SvJ strains were used for the studies. Mice were constructed that lacked a functional Dkkl1 gene. Deletion of the gene was confirmed by DNA, RNA, and protein analyses; in vivo fertility was examined by continuous mating scheme. Previous studies have shown that Dkkl1, a gene unique to mammals, is expressed predominantly, if not exclusively, in developing spermatocytes, and the DKKL1 protein accumulates in the acrosome of mature sperm. Subsequent studies (reported in the accompanying paper) demonstrate that Dkkl1 also is expressed in the trophectoderm/placental lineage. Taken together, these results strongly suggested that DKKL1 protein is required for terminal differentiation either of trophoblast giant cells or of sperm, both of which are directly involved in fertility. To challenge this hypothesis, conditional targeted mutagenesis was used to ablate the Dkkl1 gene in mice. Surprisingly, Dkkl1 nullizygous embryos developed into viable, fertile adults, despite the fact that they failed to produce any portion of the DKKL1 protein. DKKL1 is a mammalian-specific acrosomal protein that is not essential either for development or fertility.
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发表时间: 2004-03-01
影响因子: 5.3
作者:
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发表时间: 2003-03-01
期刊: GENOME RESEARCH
影响因子: 7
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发表时间: 2005-08-01
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