Mouse zinc transporter 1 gene provides an essential function during early embryonic development
Mouse zinc transporter 1 gene provides an essential function during early embryonic development
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DOI：
10.1002/gene.20067
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发表时间：
2004-10-01
期刊：
影响因子：
1.5
通讯作者：
Palmiter, RD
中科院分区：
文献类型：
--
作者：
Andrews, GK;Wang, HB;Palmiter, RD
SLC30阳离子扩散转运蛋白家族在哺乳动物中包括至少9个成员，其中大多数已被证明在锌转运中发挥作用。这个家族的创始成员，Znt1，是由于它能够从细胞中排出锌并保护它们免受锌中毒而被发现的。然而，其生理功能尚不清楚。为了解决这一问题，我们在胚胎干细胞中通过同源重组产生了靶向敲除Znt1基因的小鼠。杂合子Znt1小鼠存活。相比之下，纯合子Znt1小鼠由于胚胎发育的灾难性失败，在植入后不久就在子宫内死亡。尽管在这些胚胎周围形成了胚外膜，但胚胎本身在卵筒期之后未能进行形态发生，并且在怀孕的第9天就无定形了。Znt1基因主要表达于植后期（d5 ~ d8）滋养细胞和母体蜕膜中。纯合子Znt1胚胎发育的失败不能通过在怀孕期间操纵母亲的饮食锌（过量或缺乏）来挽救。然而，与野生型雌性相比，Znt1杂合雌性在妊娠后期暴露于母体饮食锌缺乏时，胚胎发育异常的可能性高出3倍。这些研究表明，在卵筒发育阶段，Znt1在将母体锌转运到胚胎环境中起着重要的作用，并进一步表明Znt1在成年小鼠的锌稳态中起作用。(C) 2004 Wiley-Liss, Inc。
The SLC30 family of cation diffusion transporters includes at least nine members in mammals, most of which have been documented to play a role in zinc transport. The founding member of this family, Znt1, was discovered by virtue of its ability to efflux zinc from cells and to protect them from zinc toxicity. However, its physiological functions remain unknown. To address this issue, mice with targeted knockout of the Znt1 gene were generated by homologous recombination in embryonic stem cells. Heterozygous Znt1 mice were viable. In contrast, homozygous Znt1 mice died in utero soon after implantation due to a catastrophic failure of embryonic development. Although extraembryonic membranes formed around these embryos, the embryo proper failed to undergo morphogenesis past the egg cylinder stage and was amorphous by d9 of pregnancy. Expression of the Znt1 gene was detected predominantly in trophoblasts and in the maternal deciduum during the postimplantation period (d5 to d8). The failure of homozygous Znt1 embryos to develop could not be rescued by manipulating maternal dietary zinc (either excess or deficiency) during pregnancy. However, embryos in Znt1 heterozygous females were similar to3 times more likely to develop abnormally when exposed to maternal dietary zinc deficiency during later pregnancy than were those in wildtype females. These studies suggest that Znt1 serves an essential function of transporting maternal zinc into the embryonic environment during the egg cylinder stage of development, and further suggest that Znt1 plays a role in zinc homeostasis in adult mice. (C) 2004 Wiley-Liss, Inc.