Expression of the mouse metallothionein-I and -II genes provides a reproductive advantage during maternal dietary zinc deficiency

Expression of the mouse metallothionein-I and -II genes provides a reproductive advantage during maternal dietary zinc deficiency
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DOI:
10.1093/jn/129.9.1643
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发表时间:
1999-09-01
影响因子:
4.2
通讯作者:
Geiser, J
Geiser, J
中科院分区:
医学2区
文献类型:
--
作者:
Andrews, GK;Geiser, J

文献摘要

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通过使用金属硫蛋白-I或-II(MT-I和MT-II)基因敲除(KO)的纯合小鼠来检查金属硫蛋白在锌稳态中的功能。在特定的妊娠期,给妊娠的MT-1/II KO小鼠或对照小鼠喂食缺锌(1 μ g/g或5 μ g/g)饮食或锌充足(50 μ g/g)饮食,并在妊娠第14天(第1天=阴道栓)测定对胚胎形态发生的影响。在纯合子MT-I/II KO以及非转基因对照小鼠中,从妊娠第1天开始的严重饮食锌缺乏(1 μ g/g)具有胚胎毒性酸致畸性,两种品系中的大多数胚胎在妊娠中期死亡。然而,MT-I/II KO小鼠中53%的存活胚胎形态异常,而对照小鼠中仅32%的胚胎形态异常。在随后的实验中,中度膳食锌缺乏(从怀孕第1天开始5 μ g/g或从怀孕第8天开始1 μ g/g膳食锌)会产生致畸作用,但不会产生胚胎毒性作用。MT-I/II KO小鼠中的胚胎发育异常的可能性比喂食这些相同饮食的对照小鼠中的胚胎高260%至290%。这些结果表明,MT-I和MT-II基因在怀孕女性的表达,提高了生殖成功率在母体膳食锌缺乏。
The function of metallothionein in zinc homeostasis was examined by using mice homozygous for knockout (KO) of the metallothionein-I or -II (MT-I and MT-II) genes. Pregnant MT-I/II KO mice or control mice were fed a zinc-deficient (1 mu g/g or 5 mu g/g) diet or a zinc-adequate (50 mu g/g) diet during specific periods of pregnancy, and the effects on morphogenesis of the embryos were determined at day 14 of pregnancy (day 1 = vaginal plug). In the homozygous MT-I/II KO, as well as in the nontransgenic control mice, severe dietary zinc deficiency (1 mu g/g) beginning on day 1 of pregnancy was embryotoxic acid teratogenic, and the majority of the embryos in both strains were dead by mid-gestation. However, 53% of the surviving embryos in the MT-I/II KO mice were morphologically abnormal compared to only 32% of the embryos in the control mice. In subsequent experiments, moderate dietary zinc deficiency (5 mu g/g beginning on day 1 of pregnancy or 1 mu g/g dietary zinc beginning on day 8 of pregnancy) exerted teratogenic, but not embryotoxic effects. Embryos in the MT-I/II KO mice were 260 to 290% as likely to develop abnormally than were embryos in the control mice fed these same diets. These results demonstrate that the expression of the MT-I and -II genes in pregnant females improves reproductive success during maternal dietary zinc deficiency.