Palmiter Richard D, Hammer Robert E, Brinster Ralph L
Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195.
School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Banbury Rep. 1985;20:123-132.
Human or rat growth hormone (GH) genes have been introduced into all cells of a mouse by microinjection of fertilized eggs but they were not expressed under their own promoters. However, substitution of a mouse metallothionein (MT) promoter allowed expression and regulation comparable to that of the endogenous MT genes. These fusion genes have been used to stimulate the growth of both normal mice and dwarf mice that lack sufficient GH. Substitution of a rat elastase-I promoter directed expression of GH exclusively to the acinar cells of the pancreas. Progress has been made towards developing the hGH gene into a vector that is not expressed in vivo unless an enhancer element is inserted. Recombination between overlapping DNA fragments derived from a MThGH gene, each of which is nonfunctional, has been observed when they are coinjected into mouse eggs. In some cases, functional hGH was produced as evidenced by enhanced growth of the mice.
通过向受精卵显微注射的方式,已将人类或大鼠生长激素(GH)基因导入小鼠的所有细胞中,但这些基因在其自身启动子的作用下并未表达。然而,用小鼠金属硫蛋白(MT)启动子进行替换后,可实现与内源性MT基因相当的表达和调控。这些融合基因已被用于刺激正常小鼠和缺乏足够生长激素的侏儒小鼠的生长。用大鼠弹性蛋白酶-I启动子进行替换后,可使生长激素仅在胰腺的腺泡细胞中表达。在将hGH基因开发成一种除非插入增强子元件否则不在体内表达的载体方面已取得进展。当将源自MThGH基因的重叠DNA片段(每个片段均无功能)共注射到小鼠卵中时,已观察到它们之间发生了重组。在某些情况下,小鼠生长加快证明产生了有功能的hGH。