METALLOTHIONEIN HUMAN GH FUSION GENES STIMULATE GROWTH OF MICE
METALLOTHIONEIN HUMAN GH FUSION GENES STIMULATE GROWTH OF MICE
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DOI：
10.1126/science.6356363
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发表时间：
1983-01-01
期刊：
影响因子：
56.9
通讯作者：
BRINSTER, RL
中科院分区：
文献类型：
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作者：
PALMITER, RD;NORSTEDT, G;BRINSTER, RL
将小鼠金属硫蛋白-I基因的启动子或调节区与编码人生长激素的结构基因融合。通过显微注射受精卵将这些融合基因导入小鼠体内。稳定整合融合基因的小鼠中有23只（70%）在血清中显示出高浓度的人类生长激素，并且比对照小鼠长得更大。人类生长激素的合成被镉或锌进一步诱导，这通常诱导金属硫蛋白基因的表达。表达人生长激素的转基因小鼠血清中胰岛素样生长因子I的浓度也增加。他们脑垂体的组织学显示正常合成生长激素的细胞功能紊乱。融合基因在所有组织中均有表达，但不同组织和不同动物的人生长激素信使RNA与内源性金属硫蛋白-I信使RNA的比例不同，表明外源基因的表达受整合位点和组织环境的影响。
The promoter or regulatory region of the mouse gene for metallothionein-I was fused to the structural gene coding for human growth hormone. These fusion genes were introduced into mice by microinjection of fertilized eggs. Twenty-three (70 percent) of the mice that stably incorporated the fusion genes showed high concentrations of human growth hormone in their serum and grew significantly larger than control mice. Synthesis of human growth hormone was induced further by cadmium or zinc, which normally induce metallothionein gene expression. Transgenic mice that expressed human growth hormone also showed increased concentrations of insulin-like growth factor I in their serum. Histology of their pituitaries suggests dysfunction of the cells that normally synthesize growth hormone. The fusion genes were expressed in all tissues examined, but the ratio of human growth hormone messenger RNA to endogenous metallothionein-I messenger RNA varied among different tissues and different animals, suggesting that expression of the foreign genes is influenced by site of integration and tissue environment.