Transgenic mice that overexpress metallothionein-I resist dietary zinc deficiency
Transgenic mice that overexpress metallothionein-I resist dietary zinc deficiency
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DOI：
10.1093/jn/126.4.825
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发表时间：
1996-04-01
影响因子：
4.2
通讯作者：
Andrews, GK
中科院分区：
文献类型：
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作者：
Dalton, T;Fu, K;Andrews, GK
过表达金属硫蛋白-I（MT-I）的转基因小鼠在主要器官中积累的MT-I和锌比对照小鼠多。通过给转基因小鼠和对照小鼠喂食缺锌（0.5-1.5 μ g/g）或锌充足（50 μ g/g）的饮食并通过测量对妊娠的影响来检查MT-I过表达对饮食缺锌抗性的影响。当妊娠小鼠维持在饮食锌缺乏的条件下，与对照小鼠相比，转基因小鼠的吸收和胎儿致畸缺陷的数量大大减少。转基因和对照组之间的差异不明显，在怀孕的第8天（第1天=阴道塞），但明显的第14天。这一结果表明，转基因雌性动物中较大的母体锌库允许胎儿正常发育更长时间。然而，无论是转基因或对照锌缺乏小鼠不能完成怀孕。胰腺MT浓度是最大的锌充足的转基因小鼠。此外，转基因小鼠胰腺中每克湿重的MT比检查的任何其他器官多10倍。胰腺MT浓度是锌缺乏的异常敏感的指标。胰腺MT下降了99.8%，锌下降到基础水平的D 14怀孕时，转基因小鼠和对照组小鼠喂养锌缺乏的饮食，而MT浓度在其他器官中只略有下降。我们认为，在转基因小鼠中较大的锌MT池提供了一个生物学上重要的锌不稳定池期间缺锌。
Transgenic mice that overexpress metallothionein-I (MT-I) accumulate more MT-I and zinc in major organs than do control mice. The effects of overexpression of MT-I on resistance to dietary zinc deficiency were examined by feeding transgenic and control mice a zinc-deficient (0.5-1.5 mu g/g) or a zinc-adequate (50 mu g/g) diet and by measuring effects on pregnancy. When pregnant mice were maintained under conditions of dietary zinc deficiency, the number of resorptions and teratogenic defects of fetuses was greatly reduced in transgenic compared with control mice. Differences between transgenic and controls were not apparent at d 8 of pregnancy (d 1 = vaginal plug) but were apparent by d 14. This result suggests that the larger maternal zinc pool in the transgenic females allows fetal development to progress normally for a longer period of time. However, neither transgenic nor control zinc-deficient mice could complete pregnancy. Pancreatic MT concentrations were the greatest in zinc-adequate transgenic mice. Moreover, there was >10-fold more MT per gram wet weight in the pancreas of transgenic mice than in any other organ examined. Pancreatic MT concentrations were an exceptionally sensitive indicator of zinc deficiency. Pancreatic MT declined 99.8% and zinc declined to basal levels by d 14 of pregnancy when transgenic and control mice were fed a zinc-deficient diet, whereas MT concentrations in other organs decreased only modestly. We suggest that the larger pool of zinc MT in the transgenic mice provides a biologically important labile pool of zinc during periods of zinc deficiency.