Davis B P, Hammer R E, Messing A, MacDonald R J
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9038.
J Biol Chem. 1992 Dec 25;267(36):26070-7.
Fusion genes combining the 5'-transcriptional regulatory region of the rat trypsin I gene and the structural gene of human growth hormone as a reporter were expressed to the high levels characteristic of the endogenous trypsin I gene selectively in the acinar cells of the pancreas of transgenic mice. As little as 232 base pairs of trypsin gene sequences containing the transcriptional start site and upstream promoter elements were sufficient to direct pancreatic expression. The tissue-specific expression was controlled transcriptionally. Trypsin-human growth hormone fusion transgenes also were expressed, although at low levels, in the stomach, an unexpected site for the expression of pancreatic digestive enzymes. Expression in the stomach of endogenous trypsin, elastase, and amylase genes in both normal and transgenic mice verified that transgene expression was consistent with normal expression of pancreatic genes. Endogenous amylase colocalizes with pepsinogen in the acinar cell-like Chief cells of the glandular portion of the mouse stomach. The expression of pancreatic genes in stomach cells is probably the consequence of similar developmental origins of pancreatic and gastric acinar cells from the primordial gut.
将大鼠胰蛋白酶I基因的5'-转录调控区与人生长激素结构基因融合作为报告基因的融合基因,在转基因小鼠胰腺的腺泡细胞中选择性地以内源性胰蛋白酶I基因的高水平特征进行表达。仅包含转录起始位点和上游启动子元件的232个碱基对的胰蛋白酶基因序列就足以指导胰腺表达。组织特异性表达受转录控制。胰蛋白酶-人生长激素融合转基因在胃中也有表达,尽管水平较低,胃是胰腺消化酶表达的一个意外部位。正常小鼠和转基因小鼠胃中内源性胰蛋白酶、弹性蛋白酶和淀粉酶基因的表达证实,转基因表达与胰腺基因的正常表达一致。内源性淀粉酶与胃蛋白酶原在小鼠胃腺部的腺泡样主细胞中共定位。胃细胞中胰腺基因的表达可能是胰腺和胃腺泡细胞起源于原始肠道的相似发育过程的结果。