Function and regulation of gastrin in transgenic mice: a review.
Function and regulation of gastrin in transgenic mice: a review.
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发表时间：
1992
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通讯作者：
T. Wang;S. Brand
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作者：
T. Wang;S. Brand
胃泌素基因在胎儿胰岛细胞中表达，但在成人中主要在胃窦中表达。为了研究胃泌素启动子的调控，我们创建了几个转基因，其含有与人胃泌素基因的编码序列连接的人和大鼠胃泌素5'侧翼区。人胃泌素转基因含有1，300 bp的5'侧翼DNA，而大鼠胃泌素转基因含有450 bp的5'侧翼DNA。人胃泌素转基因在胎儿胰岛中表达，但在成人胃窦中不表达。相反，大鼠胃泌素转基因在成人胃窦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，创建了嵌合胰岛素-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。将这些INS-GAS小鼠与过表达TGF α的小鼠交配，所述TGF α从小鼠金属硫蛋白转化生长因子α（MT-TGF α）转基因转录。虽然单独的胃泌素或TGF α的过表达对胰岛质量没有影响，但两种转基因的过表达导致胰岛质量增加两倍。总之，这些数据表明：（1）胃泌素可与TGF α协同相互作用以刺激胰岛生长;（2）人胃泌素转基因含有胰岛特异性增强子;（3）大鼠胃泌素转基因含有胃窦特异性增强子。
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.