Wang T C, Brand S J
Department of Medicine, Massachusetts General Hospital, Boston 02114.
Yale J Biol Med. 1992 Nov-Dec;65(6):705-13; discussion 737-40.
The gastrin gene is expressed in fetal pancreatic islet cells, but in the adult is expressed mainly in the gastric antrum. To study the regulation of the gastrin promoter, we created several transgenes containing the human and rat gastrin 5' flanking regions joined to the coding sequences of the human gastrin gene. The human gastrin transgene contained 1,300 bp of 5' flanking DNA, while the rat gastrin transgene contained 450 bp of 5' flanking DNA. The human gastrin transgene was expressed in fetal islets, but was not expressed in adult gastric antrum. In contrast, the rat gastrin transgene was expressed in adult antral G cells, but no expression was observed in fetal islets. To study the possible role of gastrin as an islet growth factor, a chimeric insulin-gastrin (INS-GAS) transgene was created, in which the expression of the human gastrin gene is driven from the rat insulin I promoter. These INS-GAS mice were mated with mice overexpressing TGF alpha, transcribed from a mouse metallothionein-transforming growth factor alpha (MT-TGF alpha) transgene. While overexpression of gastrin or TGF alpha alone had no effect on islet mass, overexpression of both transgenes resulted in a twofold increase in islet mass. In conclusion, these data indicate that (1) gastrin can interact synergistically with TGF alpha to stimulate islet growth; (2) the human gastrin transgene contains the islet specific enhancer; (3) the rat gastrin transgene contains the antral specific enhancer.
胃泌素基因在胎儿胰岛细胞中表达，但在成体中主要在胃窦中表达。为了研究胃泌素启动子的调控，我们构建了几个转基因，它们包含与人胃泌素基因编码序列相连的人和大鼠胃泌素5'侧翼区。人胃泌素转基因包含1300 bp的5'侧翼DNA，而大鼠胃泌素转基因包含450 bp的5'侧翼DNA。人胃泌素转基因在胎儿胰岛中表达，但在成体胃窦中不表达。相反，大鼠胃泌素转基因在成体胃窦G细胞中表达，但在胎儿胰岛中未观察到表达。为了研究胃泌素作为胰岛生长因子的可能作用，构建了一个嵌合胰岛素-胃泌素（INS-GAS）转基因，其中人胃泌素基因的表达由大鼠胰岛素I启动子驱动。这些INS-GAS小鼠与过表达TGFα的小鼠交配，TGFα由小鼠金属硫蛋白-转化生长因子α（MT-TGFα）转基因转录而来。虽然单独过表达胃泌素或TGFα对胰岛质量没有影响，但两个转基因的过表达导致胰岛质量增加了两倍。总之这些数据表明：（1）胃泌素可与TGFα协同作用以刺激胰岛生长；（2）人胃泌素转基因包含胰岛特异性增强子；（3）大鼠胃泌素转基因包含胃窦特异性增强子。
